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Taylor L, McCaddon A, Wolffenbuttel BHR. Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid. Nutrients 2024; 16:662. [PMID: 38474790 DOI: 10.3390/nu16050662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 02/18/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
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.
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Affiliation(s)
- Lori Taylor
- Faculty of Integrative and Functional Nutrition, Saybrook University, Pasadena, CA 91103, USA
| | - Andrew McCaddon
- Faculty of Social and Life Sciences, Wrexham University, Wrexham LL11 2AW, UK
| | - Bruce H R Wolffenbuttel
- University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
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2
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Atzeni F, Palumbo A, Boccassini L, Sarzi-Puttini P. Helicobacter pylori Infection and Gastric Autoimmunity. INFECTION AND AUTOIMMUNITY 2024:459-471. [DOI: 10.1016/b978-0-323-99130-8.00023-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Shah SC, Boeder S, Piazuelo MB, Li D. The Stomach Looks Suspicious, But Is It Pernicious? Gastroenterology 2023; 165:1342-1351. [PMID: 37640254 PMCID: PMC11058005 DOI: 10.1053/j.gastro.2023.08.032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Revised: 08/18/2023] [Accepted: 08/18/2023] [Indexed: 08/31/2023]
Affiliation(s)
- Shailja C Shah
- Gastroenterology Section, Jennifer Moreno Department of Veterans Affairs Medical Center, La Jolla, California; Division of Gastroenterology, University of California, San Diego, La Jolla, California.
| | - Schafer Boeder
- Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California
| | - M Blanca Piazuelo
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee; Center for Mucosal Inflammation and Cancer, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Dan Li
- Department of Gastroenterology, Kaiser Permanente Northern California, Santa Clara, California; Division of Research, Kaiser Permanente Northern California, Oakland, California
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4
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Dottori L, Pivetta G, Annibale B, Lahner E. Update on Serum Biomarkers in Autoimmune Atrophic Gastritis. Clin Chem 2023; 69:1114-1131. [PMID: 37680186 DOI: 10.1093/clinchem/hvad082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 05/05/2023] [Indexed: 09/09/2023]
Abstract
BACKGROUND Autoimmune atrophic gastritis (AAG) is a persistent, corpus-restricted immune-mediated destruction of the gastric corpus oxyntic mucosa with reduced gastric acid and intrinsic factor secretion, leading to iron deficiency and pernicious anemia as a consequence of iron and cobalamin malabsorption. Positivity toward parietal cell (PCA) and intrinsic factor (IFA) autoantibodies is very common. AAG may remain asymptomatic for many years, thus making its diagnosis complex and often delayed. Due to the increased risk of gastric neoplasms, a timely diagnosis of AAG is clinically important. CONTENT The gold standard for AAG diagnosis is histopathological assessment of gastric biopsies obtained during gastroscopy, but noninvasive, preendoscopic serological screening may be useful in some clinical scenarios. Serum biomarkers for AAG may be divided into 2 groups: gastric autoimmunity-related biomarkers, such as PCA and IFA, and gastric corpus atrophy/reduced gastric acid secretion-related biomarkers, such as serum gastrin and pepsinogens. The present review focuses on the clinical significance and pitfalls of serum biomarkers related to gastric autoimmunity and gastric corpus atrophy, including some discussion of analytical methods. SUMMARY Serum assays for PCA, IFA, gastrin, and pepsinogen I show good diagnostic accuracy for noninvasive diagnostic work-up of AAG. Diagnostic performance may increase by combining >1 of these tests, overcoming the problem of seronegative AAG. However, appropriately designed, comparative studies with well-characterized patient cohorts are needed to better define the reliability of these biomarkers in the diagnosis of patients with AAG. Currently, positive serum tests should always be followed by the state-of-art diagnostic test, that is, histopathological assessment of gastric biopsies obtained during gastroscopy to definitively confirm or rule out AAG and eventually neoplastic complications.
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Affiliation(s)
- Ludovica Dottori
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Giulia Pivetta
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Bruno Annibale
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
| | - Edith Lahner
- Department of Medical-Surgical Sciences and Translational Medicine, Sant'Andrea Teaching Hospital, Sapienza University of Rome, Rome, Italy
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Busebee BT, Zhong Q, Murray JA. 50-Year-Old Man With Hematochezia and Fatigue. Mayo Clin Proc 2023; 98:332-336. [PMID: 36737121 DOI: 10.1016/j.mayocp.2022.05.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Revised: 05/10/2022] [Accepted: 05/19/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Bradley T Busebee
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Qiaonan Zhong
- Resident in Internal Medicine, Mayo Clinic School of Graduate Medical Education, Rochester, MN
| | - Joseph A Murray
- Advisor to residents and Consultant in Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
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Apolinario M, Brussels A, Cook CB, Yang S. Autoimmune polyglandular syndrome type 3: A case report of an unusual presentation and literature review. Clin Case Rep 2022; 10:e05391. [PMID: 35140971 PMCID: PMC8815091 DOI: 10.1002/ccr3.5391] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Revised: 12/20/2021] [Accepted: 01/14/2022] [Indexed: 11/11/2022] Open
Abstract
Autoimmune polyglandular syndromes (APS) are rare disorders characterized by auto-destruction of endocrine and non-endocrine organs by organ-specific antibody-directed T-lymphocytic infiltration. This case highlights a 29-year-old Caucasian man with vitiligo found to have significant neurological abnormalities in the setting of newly diagnosed pernicious anemia and thyroid autoimmune disease.
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Affiliation(s)
- Michael Apolinario
- Department of Internal MedicineMayo Clinic College of Medicine and ScienceScottsdaleArizonaUSA
| | - Aaron Brussels
- Department of Anesthesiology and Perioperative MedicineMayo Clinic College of Medicine and ScienceScottsdaleArizonaUSA
| | - Curtiss B. Cook
- Division of EndocrinologyDepartment of Internal MedicineMayo Clinic College of Medicine and ScienceScottsdaleArizonaUSA
| | - Shaun Yang
- Division of Hospital Internal MedicineDepartment of Internal MedicineMayo Clinic College of Medicine and ScienceScottsdaleArizonaUSA
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Wolffenbuttel BHR, Muller Kobold AC, Sobczyńska-Malefora A, Harrington DJ. Macro-B12 masking B12 deficiency. BMJ Case Rep 2022; 15:15/1/e247660. [PMID: 35027389 PMCID: PMC8762123 DOI: 10.1136/bcr-2021-247660] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
In clinical practice, the finding of an elevated serum B12 concentration is often the consequence of supplementation with B12 in either oral form or injections. Also, elevated serum B12 may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B12-vitamin binding proteins with immunoglobulins, the so-called macro-B12. We describe a young woman who previously was diagnosed with B12 deficiency, and in whom, after cessation of B12 injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B12 concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B12, which not only resulted in erroneous and longstanding elevated serum B12, but also masked her underlying B12 deficiency.
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Affiliation(s)
- Bruce H R Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Anneke C Muller Kobold
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Agata Sobczyńska-Malefora
- Faculty of Life Sciences and Medicine, King's College London, London, UK
- Nutristasis Unit, Viapath, St Thomas' Hospital, London, UK
| | - Dominic J Harrington
- Faculty of Life Sciences and Medicine, King's College London, London, UK
- Nutristasis Unit, Viapath, St Thomas' Hospital, London, UK
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8
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Marzinotto I, Dottori L, Baldaro F, Dilaghi E, Brigatti C, Bazzigaluppi E, Esposito G, Davidson HW, Piemonti L, Lampasona V, Lahner E. Intrinsic factor autoantibodies by luminescent immuno-precipitation system in patients with corpus atrophic gastritis. J Transl Autoimmun 2022; 4:100131. [PMID: 35005595 PMCID: PMC8716657 DOI: 10.1016/j.jtauto.2021.100131] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 10/28/2021] [Accepted: 10/29/2021] [Indexed: 11/30/2022] Open
Abstract
Background Corpus atrophic gastritis (CAG) may lead to intrinsic factor (IF) deficiency and vitamin B12 malabsorption. Intrinsic factor autoantibodies (IFA) are considered markers of pernicious anemia, but their clinical utility in CAG has not been evaluated. This study aimed to assess IFA in CAG patients and controls using a luciferase immunoprecipitation system (LIPS). Methods Recombinant nanoluciferase-tagged IF secreted from transfected Expi293F cells was used as antigen in an IFA-LIPS assay. IFA IgG were measured in sera from subjects undergoing gastroscopy and biopsy (updated Sydney system) mainly for anemia (57%) or dyspepsia (34%). This cohort comprised 105 patients with histologically-proven-CAG (cases: median age 64 years, 68% females) and 110 subjects with suspected CAG that were histologically negative (controls: median age 67 years, 54% females). Cut-off values were selected by Q-Q-plot analysis (negative: <2.5 arbitrary units). Results IFA levels were higher in cases than in controls (Mann-Whitney:p < 10−5). The ROC-AUC was 0.67 (95%CI 0.60–0.73, p < 0.0001). The IFA LIPS sensitivity and specificity for CAG were 32% (95% CI 24–42) and 95% (95% CI 90–99). This diagnostic performance remained similar after stratification for the presence/absence of anemia, dyspepsia or vitamin B12 deficiency. IFA levels were higher in females compared with males (p = 0.0127). In females aged <65 years, IFA-positives were more prevalent than in males (43.5% vs 6.6%, p = 0.011). Conclusions The IFA-LIPS assay discriminated between CAG patients and controls showing a good specificity (95%) at the cost of sensitivity (32%). IFA-positivity occurred independently from anemia and vitamin B12 deficiency, but was more frequent in younger females. IFA testing should be considered in patients at high clinical suspicion of CAG.
A novel diagnostic autoantibody test for intrinsic factor autoantibodies using a LIPS in histologically-proven CAG patients and controls. This assay discriminated between patients and controls with a good specificity and a relatively low sensitivity that reflects the likely low prevalence of intrinsic factor antibodies in CAG. Positivity occurred independently from anemia and vitamin B12 deficiency. Intrinsic factor antibodies should be assessed in patients at high clinical suspicion of CAG.
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Affiliation(s)
- Ilaria Marzinotto
- San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Ludovica Dottori
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Francesca Baldaro
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Emanuele Dilaghi
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Cristina Brigatti
- San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Elena Bazzigaluppi
- San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Gianluca Esposito
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
| | - Howard W Davidson
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Lorenzo Piemonti
- San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Vito Lampasona
- San Raffaele Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Edith Lahner
- Medical-Surgical Department of Clinical Sciences and Translational Medicine, Sant'Andrea Hospital, School of Medicine, University Sapienza, Rome, Italy
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Torrez M, Chabot-Richards D, Babu D, Lockhart E, Foucar K. How I investigate acquired megaloblastic anemia. Int J Lab Hematol 2022; 44:236-247. [PMID: 34981651 DOI: 10.1111/ijlh.13789] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 10/20/2021] [Indexed: 12/01/2022]
Abstract
In this review of megaloblastic anemia (MA), an overview of vitamin B12 and folate body requirements, biochemical pathways, and laboratory testing strategies will be provided. However, the focus of this review is the classic and unique features of MA in blood and bone marrow. Acquired MA is a benign disorder for many, but can be detrimental for some. The clinical presentation can vary considerably, and the spectrum of symptoms and signs is diverse and quite broad. Prompt recognition and therapy are critical to prevent potential irreversible damage and clinical sequelae, especially in patients with vitamin B12 deficiency. A delay in diagnosis of vitamin B12 deficiency can result in significant neurologic sequelae that may not fully resolve with treatment, including in neonates and young infants. The blood and bone marrow features in MA can closely mimic thrombocytopenic purpura, myelodysplasia, and other myeloid neoplasms. Both pancytopenia and normal MCV at presentation are common in MA and raise unique challenges for the diagnostician. Partially treated MA is also a significant diagnostic "trap". MA is highly responsive to treatment, and patients tend to improve rapidly upon treatment initiation. However, the broad range of clinical and hematologic features makes the rapid, successful diagnosis of MA a unique challenge for the hematopathologist. Even in the era of state-of-the-art laboratory testing, a high suspicion is required.
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Affiliation(s)
- Mary Torrez
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Devon Chabot-Richards
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Daniel Babu
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Evelyn Lockhart
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
| | - Kathryn Foucar
- Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
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10
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Htut TW, Thein KZ, Oo TH. Pernicious anemia: Pathophysiology and diagnostic difficulties. J Evid Based Med 2021; 14:161-169. [PMID: 34015185 DOI: 10.1111/jebm.12435] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 04/28/2021] [Indexed: 11/29/2022]
Abstract
Pernicious anemia (PA) is the most common cause of vitamin B12 (cobalamin) deficiency anemia in the world. It is an autoimmune disease, comprising of salient features of autoimmune chronic atrophic gastritis (CAG) and cobalamin deficiency (CD). Although the anemia was first described as pernicious, it may well be controlled with vitamin B12 replacement. The onset and progression of PA is often insidious. Alternatively, patients may have no anemic symptoms since they become acclimatized to the subtle nature of the disease. Oftentimes, there is a possibility that the underlying disease may be missed unless a full blood count (FBC) is investigated, leading to hindrance in the treatment journey. Diagnostic challenges remain tangible for many practicing clinicians, since there is lack of reliable cobalamin assays to diagnose CD as well as clinical mimics, which simulate many other hematological conditions, such as myelodysplastic syndrome, acute leukemia, sideroblastic anemias, bone marrow failure states, thrombotic microangiopathy, and thromboembolism. Moreover, prompt recognition of the symptoms of CD is also vital, because some neurologic sequalae may become irreversible despite replenishing cobalamin. Herein, we discuss a literature review on the pathophysiology, challenging clinical presentations and diagnostic difficulties of PA. Since the cobalamin replacement therapy for PA is straightforward, it will not be discussed in this review.
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Affiliation(s)
- Thura Win Htut
- Department of Hematology, Aberdeen Royal Infirmary Hospital, The University of Aberdeen, NHS Grampian, Scotland, UK
| | - Kyaw Zin Thein
- Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA
| | - Thein Hlaing Oo
- Section of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, USA
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11
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Alwasaidi TA, Mustafa W, Osman H, Al-Hebshi A, Alfetayeh A. Multiple Autoimmune Syndrome With Alopecia Universalis and Immune Thrombocytopenic Purpura. Cureus 2021; 13:e13033. [PMID: 33665054 PMCID: PMC7924964 DOI: 10.7759/cureus.13033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/31/2021] [Indexed: 11/05/2022] Open
Abstract
Multiple autoimmune syndrome (MAS) is a condition characterized by three or more autoimmune disorders in the same individual. The development of MAS involves genetic, immunological, and infectious factors. Here we report a case of a 40-year-old man who presented with four autoimmune diseases, namely autoimmune hypothyroidism, alopecia universalis, celiac disease, and immune thrombocytopenic purpura (ITP), which leads to a diagnosis of MAS. However, the patient does not fit in any category of MAS classification. In addition to the need for continued surveillance for the development of new autoimmune disease in predisposed patients, this case report suggests an additional fourth category of the classification of MAS that includes autoimmune hypothyroidism, alopecia universalis, celiac disease, and ITP.
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Affiliation(s)
- Turki A Alwasaidi
- Hematology Division/Internal Medicine Department, Prince Mohammed Bin Abdulaziz Hospital - Ministry of National Guard Health Affairs, Madinah, SAU
- Internal Medicine, Taibah University, Madinah, SAU
| | | | - Haitham Osman
- Hematology Division/Internal Medicine Department, Prince Mohammed Bin Abdulaziz Hospital - Ministry of National Guard Health Affairs, Madinah, SAU
| | - Abdulqader Al-Hebshi
- Pediatrics-Hematology Oncology, Prince Mohammed Bin Abdulaziz Hospital, Madinah, SAU
- Pediatrics, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, SAU
| | - Asma Alfetayeh
- Hematology, Prince Mohammed Bin Abdulaziz Hospital, Madinah, SAU
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Lee KT, Teoh CS, Chew TK, Goh AS. Microangiopathic haemolytic anaemia and thrombocytopenia due to combined vitamin B12 and folate deficiency masquerading as thrombotic thrombocytopenic purpura. J R Coll Physicians Edinb 2020; 50:144-147. [PMID: 32568285 DOI: 10.4997/jrcpe.2020.213] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Vitamin B12 deficiency and folate deficiency are common causes of macrocytic anaemia and both are important for many cellular processes. These deficiencies could be due to inadequate dietary intake, impaired absorption or drug ingestion. We present a case of a 47-year-old male with a history of diffuse large B-cell lymphoma (DLBCL) who was admitted for fatigue, persistent frontal headache and left upper-quadrant abdominal pain. Further investigation showed that he had pancytopenia with microangiopathic haemolytic anaemia (MAHA) and intracranial bleeding (ICB). Serum vitamin B12 and folate were later found to be low and a diagnosis of combined vitamin B12 and folate deficiency mimicking thrombotic thrombocytopenic purpura (TTP) was made. The patient responded well to vitamin B12 and folate replacement.
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Affiliation(s)
- Kee Tat Lee
- Department of Medicine, Hospital Pulau Pinang, Jalan Residensi, 10990 Georgetown, Pulau Pinang, Malaysia,
| | - Ching Soon Teoh
- Hematology unit, Department of Medicine, Hospital Pulau Pinang, Pulau Pinang, Malaysia
| | - Teng Keat Chew
- Hematology unit, Department of Medicine, Hospital Pulau Pinang, Pulau Pinang, Malaysia
| | - Ai Sim Goh
- Hematology unit, Department of Medicine, Hospital Pulau Pinang, Pulau Pinang, Malaysia
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Wienholt L, Dawson E, Khan L, Hughes T, Lee F. The impact of indirect immunofluorescence screening dilution on the positivity of gastric parietal cell antibodies. Pathology 2020; 52:589-590. [PMID: 32580892 DOI: 10.1016/j.pathol.2020.04.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 04/14/2020] [Accepted: 04/22/2020] [Indexed: 10/24/2022]
Affiliation(s)
- Louise Wienholt
- The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP), St Leonards, Sydney, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
| | - Emma Dawson
- The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP), St Leonards, Sydney, Australia
| | - Loriza Khan
- The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP), St Leonards, Sydney, Australia
| | - Tiffany Hughes
- Clinical Immunology and Allergy Department, The Royal Adelaide Hospital, Adelaide, Australia
| | - Frederick Lee
- Sydney Medical School, University of Sydney, Sydney, Australia; Department of Clinical Immunology and Allergy, Royal Prince Alfred Hospital, Sydney, Australia
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14
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15
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Iftikhar H, Saleem M, Kaji A. Pernicious Anemia Presenting as Non-ST-elevated Myocardial Infarction and Depression. Cureus 2019; 11:e4870. [PMID: 31417815 PMCID: PMC6687429 DOI: 10.7759/cureus.4870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Pernicious anemia (PA) is a common cause of megaloblastic anemia throughout the world, especially in Northern European whites. This disease is characterized by the deficiency of vitamin B12 due to the presence of anti-intrinsic factor and anti-parietal cell antibodies which inhibit the absorption of the vitamin B12. In cases of severe vitamin B12 deficiency, patients can suffer debilitating complications such as described in our case.
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Affiliation(s)
- Hassaan Iftikhar
- Internal Medicine, St. Francis Medical Center, Seton Hall University, Trenton, USA
| | - Maryam Saleem
- Internal Medicine, Waterbury Hospital, Waterbury, USA
| | - Anand Kaji
- Internal Medicine, St. Francis Medical Center, Seton Hall University, Trenton, USA
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Wolffenbuttel BH, Wouters HJ, Heiner-Fokkema MR, van der Klauw MM. The Many Faces of Cobalamin (Vitamin B 12) Deficiency. Mayo Clin Proc Innov Qual Outcomes 2019; 3:200-214. [PMID: 31193945 PMCID: PMC6543499 DOI: 10.1016/j.mayocpiqo.2019.03.002] [Citation(s) in RCA: 124] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic megaloblastic anemia. In clinical practice, many cases of vitamin B12 deficiency are overlooked or sometimes even misdiagnosed. In this review, we describe the heterogeneous disease spectrum of patients with vitamin B12 deficiency in whom the diagnosis was either based on low serum B12 levels, elevated biomarkers like methylmalonic acid and/or homocysteine, or the improvement of clinical symptoms after the institution of parenteral vitamin B12 therapy. We discuss the possible clinical signs and symptoms of patients with B12 deficiency and the various pitfalls of diagnosis and treatment.
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Affiliation(s)
- Bruce H.R. Wolffenbuttel
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - Hanneke J.C.M. Wouters
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
- Department of Haematology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - M. Rebecca Heiner-Fokkema
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
| | - Melanie M. van der Klauw
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, NL-9700 RB, The Netherlands
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Kozhakhmetova A, Wyatt RC, Caygill C, Williams C, Long AE, Chandler K, Aitken RJ, Wenzlau JM, Davidson HW, Gillespie KM, Williams AJK. A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study. Clin Exp Immunol 2018; 192:251-258. [PMID: 29431870 DOI: 10.1111/cei.13115] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2018] [Indexed: 12/28/2022] Open
Abstract
Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.
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Affiliation(s)
- A Kozhakhmetova
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - R C Wyatt
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - C Caygill
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - C Williams
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - A E Long
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - K Chandler
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - R J Aitken
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - J M Wenzlau
- The Barbara Davis Center for Diabetes, University of Colorado, Denver, CO, USA
| | - H W Davidson
- The Barbara Davis Center for Diabetes, University of Colorado, Denver, CO, USA
| | - K M Gillespie
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
| | - A J K Williams
- Diabetes and Metabolism, Translational Health Sciences, University of Bristol, Bristol, UK
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19
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Autoimmunity and Gastric Cancer. Int J Mol Sci 2018; 19:ijms19020377. [PMID: 29373557 PMCID: PMC5855599 DOI: 10.3390/ijms19020377] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2017] [Revised: 01/23/2018] [Accepted: 01/24/2018] [Indexed: 12/27/2022] Open
Abstract
Alterations in the immune response of patients with autoimmune diseases may predispose to malignancies, and a link between chronic autoimmune gastritis and gastric cancer has been reported in many studies. Intestinal metaplasia with dysplasia of the gastric corpus-fundus mucosa and hyperplasia of chromaffin cells, which are typical features of late-stage autoimmune gastritis, are considered precursor lesions. Autoimmune gastritis has been associated with the development of two types of gastric neoplasms: intestinal type and type I gastric carcinoid. Here, we review the association of autoimmune gastritis with gastric cancer and other autoimmune features present in gastric neoplasms.
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Harakal J, Rival C, Qiao H, Tung KS. Regulatory T Cells Control Th2-Dominant Murine Autoimmune Gastritis. THE JOURNAL OF IMMUNOLOGY 2016; 197:27-41. [PMID: 27259856 DOI: 10.4049/jimmunol.1502344] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2015] [Accepted: 04/18/2016] [Indexed: 12/12/2022]
Abstract
Pernicious anemia and gastric carcinoma are serious sequelae of autoimmune gastritis (AIG). Our study indicates that in adult C57BL/6-DEREG mice expressing a transgenic diphtheria toxin receptor under the Foxp3 promoter, transient regulatory T cell (Treg) depletion results in long-lasting AIG associated with both H(+)K(+)ATPase and intrinsic factor autoantibody responses. Although functional Tregs emerge over time during AIG occurrence, the effector T cells rapidly become less susceptible to Treg-mediated suppression. Whereas previous studies have implicated dysregulated Th1 cell responses in AIG pathogenesis, eosinophils have been detected in gastric biopsy specimens from patients with AIG. Indeed, AIG in DEREG mice is associated with strong Th2 cell responses, including dominant IgG1 autoantibodies, elevated serum IgE, increased Th2 cytokine production, and eosinophil infiltration in the stomach-draining lymph nodes. In addition, the stomachs exhibit severe mucosal and muscular hypertrophy, parietal cell loss, mucinous epithelial cell metaplasia, and massive eosinophilic inflammation. Notably, the Th2 responses and gastritis severity are significantly ameliorated in IL-4- or eosinophil-deficient mice. Furthermore, expansion of both Th2-promoting IFN regulatory factor 4(+) programmed death ligand 2(+) dendritic cells and ILT3(+) rebounded Tregs was detected after transient Treg depletion. Collectively, these data suggest that Tregs maintain physiological tolerance to clinically relevant gastric autoantigens, and Th2 responses can be a pathogenic mechanism in AIG.
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Affiliation(s)
- Jessica Harakal
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908; and
| | - Claudia Rival
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908; and Department of Pathology, University of Virginia, Charlottesville, VA 22908
| | - Hui Qiao
- Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908; and Department of Pathology, University of Virginia, Charlottesville, VA 22908
| | - Kenneth S Tung
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908; Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908; and Department of Pathology, University of Virginia, Charlottesville, VA 22908
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21
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Kim J, Kim MJ, Kho HS. Oral manifestations in vitamin B12 deficiency patients with or without history of gastrectomy. BMC Oral Health 2016; 16:60. [PMID: 27234214 PMCID: PMC4884371 DOI: 10.1186/s12903-016-0215-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Accepted: 05/18/2016] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The purpose of this study was to compare clinical features of vitamin B12 deficiency patients with a history of gastrectomy to those without a history of gastrectomy. METHODS Twenty-two patients with vitamin B12 deficiency were included. Patients' chief complaints, oral manifestations, blood examination results, and past medical histories were reviewed. RESULTS Eleven patients had a history of gastrectomy and 11 did not. The chief complaint was glossodynia in all patients. No significant differences were observed between the two groups regarding age, sex, symptom duration, or plasma vitamin B12 level. Erythema and depapillation of the tongue were the most common findings, however less common among patients without a history of gastrectomy. Two patients with a history of gastrectomy and 5 patients without a history of gastrectomy had normal oral mucosa. Patients with a history of gastrectomy were more anemic. Oral symptoms of the majority of patients responded to antifungals and vitamin B12 replacement. The suggested etiologies for vitamin B12 deficiency in the patients without a history of gastrectomy were gastritis, medications, diet, autoimmunity, and early gastric cancer. CONCLUSIONS Vitamin B12 deficiency and its associated etiological factors should be considered in patients with glossodynia, even those whose oral mucosa appears normal and who lack a history of gastrectomy.
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Affiliation(s)
- Jihoon Kim
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, Yunkeun-Dong 28, Chongro-Ku, Seoul, 110-749, Republic of Korea
| | - Moon-Jong Kim
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, Yunkeun-Dong 28, Chongro-Ku, Seoul, 110-749, Republic of Korea
| | - Hong-Seop Kho
- Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, Yunkeun-Dong 28, Chongro-Ku, Seoul, 110-749, Republic of Korea. .,Institute on Aging, Seoul National University, Gwanak-Ro 1, Gwanak-Gu, Seoul, 151-742, Republic of Korea.
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22
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Wenzlau JM, Fain PR, Gardner TJ, Frisch LM, Annibale B, Hutton JC. ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study. Diabetes Care 2015; 38 Suppl 2:S29-S36. [PMID: 26405069 PMCID: PMC4582907 DOI: 10.2337/dcs15-2006] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Accepted: 07/04/2015] [Indexed: 02/05/2023]
Abstract
Autoantibodies targeting the H+/K+-ATPase proton pump of the gastric parietal cell (parietal cell antibodies [PCA]) are diagnostic of atrophic body gastritis (ABG) leading to pernicious anemia (PA). PCA, ABG, and PA occur in increased frequency in patients with type 1 diabetes and their relatives and are considered "minor" components of forms of autoimmune polyglandular syndrome (APS). A customized radioimmunoprecipitation assay was applied to 6,749 samples from the Type 1 Diabetes Genetics Consortium to measure ATP4A autoreactivity. Autoantibody prevalence was correlated with variants in HLA class II, PTPN22, and CTLA4 genes. With an ATP4A radioimmunoprecipitation assay, PCA were detected in sera from 20.9% of affected individuals. PCA prevalence increased with age and was greater in females (25.3%) than males (16.5%) and among Hispanics (36.3%) and blacks (26.2%) compared with non-Hispanic whites (20.8%) and Asians (16.7%). PCA and other organ-specific autoantibodies GAD65, IA-2, thyroid peroxidase (TPO), 21-hydroxylase (21-OH), and transglutaminase (TG) clustered within families with heritability estimates from 71 to 95%. PCA clustered with TPO, 21-OH, and persistent GAD65 autoantibodies but not with celiac (TG) or IA-2 autoantibodies. PCA-positive subjects showed an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T). Genetic variants accounted for 4-5% of the heritable risk for PCA. The same alleles were associated with other autoantibody phenotypes in a consistent pattern. Whereas most of the heritable risk for PCA and other antibodies reflects genetic effects that are tissue specific, parietal cell autoimmunity is a major pathogenetic contributor in APS2.
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Affiliation(s)
- Janet M Wenzlau
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO
| | - Pamela R Fain
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO
| | - Thomas J Gardner
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO
| | - Lisa M Frisch
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO
| | - Bruno Annibale
- Digestive and Liver Disease Unit, University "La Sapienza," Sant'Andrea Hospital, Rome, Italy
| | - John C Hutton
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO
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23
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Kakleas K, Soldatou A, Karachaliou F, Karavanaki K. Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM). Autoimmun Rev 2015; 14:781-97. [PMID: 26001590 DOI: 10.1016/j.autrev.2015.05.002] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Accepted: 05/06/2015] [Indexed: 12/16/2022]
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24
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Osborne D, Sobczyńska-Malefora A. Autoimmune mechanisms in pernicious anaemia & thyroid disease. Autoimmun Rev 2015; 14:763-8. [PMID: 25936607 DOI: 10.1016/j.autrev.2015.04.011] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 04/23/2015] [Indexed: 12/15/2022]
Abstract
Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels.
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25
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Management and disease outcome of type I gastric neuroendocrine tumors: the Mount Sinai experience. Dig Dis Sci 2015; 60:996-1003. [PMID: 25399327 DOI: 10.1007/s10620-014-3410-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2014] [Accepted: 10/17/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM The incidence of gastric neuroendocrine tumors (NETs) has increased tenfold since the 1970s. Our aim was to describe the clinicopathologic profile, management, and outcomes of type I gastric NETs at The Mount Sinai Hospital. METHODS From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56 patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to 2012. We generated a comprehensive dataset encompassing demographic, clinical, endoscopic, and pathologic factors. Survival information was determined from medical records and the Social Security Death Index. Tumor-node-metastasis staging was conducted, and tumors were graded based on mitotic counts and Ki67 index. RESULTS Median NET size was 3.0 mm; 55.8 % displayed multifocal disease. Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %, respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade. Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 % underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical resection. 5- and 10-year disease-specific survival was 100 %. CONCLUSIONS Most patients received annual endoscopic surveillance, with a minority undergoing surgical resection, though outcomes remained excellent independent of therapeutic approach. We identified a very low but real rate of loco-regional spread, despite the generally indolent behavior of type I gastric NETs. Several patients demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of regular endoscopic management not only for gastric NETs, but also for dysplasia and adenocarcinoma.
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26
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Varbanova M, Frauenschläger K, Malfertheiner P. Chronic gastritis - an update. Best Pract Res Clin Gastroenterol 2014; 28:1031-42. [PMID: 25439069 DOI: 10.1016/j.bpg.2014.10.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2014] [Revised: 10/14/2014] [Accepted: 10/21/2014] [Indexed: 01/31/2023]
Abstract
Helicobacter pylori is the main aetiologic factor for chronic gastritis worldwide. The degree of inflammation and the evolution of this form of chronic gastritis can vary largely depending on bacterial virulence factors, host susceptibility factors and environmental conditions. Autoimmune gastritis is another cause of chronic inflammation in the stomach, which can occur in all age groups. This disease presents typically with vitamin B12 deficiency and pernicious anaemia. The presence of anti-parietal cell antibodies is highly specific for the diagnosis. The role of H. pylori as a trigger for autoimmune gastritis remains uncertain. Other rare conditions for chronic gastritis are chronic inflammatory conditions such as Crohn's disease or on the background of lymphocytic or collagenous gastroenteropathies.
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Affiliation(s)
- Mariya Varbanova
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Katrin Frauenschläger
- Institute of Pathology, Otto-von-Guericke University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University of Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.
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27
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Gonçalves C, Oliveira ME, Palha AM, Ferrão A, Morais A, Lopes AI. Autoimmune gastritis presenting as iron deficiency anemia in childhood. World J Gastroenterol 2014; 20:15780-15786. [PMID: 25400463 PMCID: PMC4229544 DOI: 10.3748/wjg.v20.i42.15780] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To characterize clinical, laboratorial, and histological profile of pediatric autoimmune gastritis in the setting of unexplained iron deficiency anemia investigation.
METHODS: A descriptive, observational study including pediatric patients with a diagnosis of autoimmune gastritis (positive parietal cell antibody and gastric corpus atrophy) established in a 6 year period (2006-2011) in the setting of refractory iron deficiency anemia (refractoriness to oral iron therapy for at least 6 mo and requirement for intravenous iron therapy) investigation, after exclusion of other potentially contributing causes of anemia. Helicobacter pylori (H. pylori) infection and anti-secretory therapy were also excluded. Data were retrospectively collected from clinical files, including: demographic data (age, gender, and ethnic background), past medical history, gastrointestinal symptoms, familial history, laboratorial evaluation (Hb, serum ferritin, serum gastrin, pepsinogen I/ pepsinogen II, B12 vitamin, intrinsic factor autoantibodies, thyroid autoantibodies, and anti-transglutaminase antibodies), and endoscopic and histological findings (HE, Periodic Acid-Schiff/Alcian blue, gastrin, chromogranin A and immunochemistry analysis for CD3, CD20 and CD68). Descriptive statistical analysis was performed (mean, median, and standard deviation).
RESULTS: We report a case-series concerning 3 girls and 2 boys with a mean age of 13.6 ± 2.8 years (3 Caucasian and 2 African). One girl had type I diabetes. Familial history was positive in 4/5 cases, respectively for autoimmune thyroiditis (2/5), sarcoidosis (1/5) and multiple myeloma (1/5). Laboratorial evaluation on admission included: Hb: 9.5 ± 0.7 g/dL; serum ferritin: 4.0 ± 0.9 ng/mL; serum gastrin: 393 ± 286 pg/mL; low pepsinogen I/ pepsinogen II ratio in 1/5 patients; normal vitamin B12 levels (analyzed in 3 patients). Endoscopy findings included: duodenal nodularity (2/5) and gastric fold softening (2/5), and histological evaluation showed corpus atrophic gastritis with lymphocytic infiltration (5/5), patchy oxyntic gland mononuclear cell infiltration (5/5), intestinal and/or pseudo-pyloric metaplasia in corpus mucosa (4/5), and enterochromaffin cell hyperplasia (4/5). Immunochemistry for gastrin on corpus biopsies was negative in all cases. Duodenal histology was normal. All biopsies were negative for H. pylori (Giemsa staining and cultural examination).
CONCLUSION: We highlight autoimmune gastritis as a diagnosis to be considered when investigating refractory iron deficiency anemia in children, particularly in the setting of a personal/familial history of autoimmune disease, as well as the diagnostic contribution of a careful immunohistological evaluation.
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28
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Hirokawa M. [Recent progress of diagnosis and treatment for immune-mediated hematological diseases. Topics: III. Diagnosis and treatment: 3. Pernicious anemia]. ACTA ACUST UNITED AC 2014; 103:1609-12. [PMID: 25154255 DOI: 10.2169/naika.103.1609] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol 2014; 166:496-513. [PMID: 24942828 DOI: 10.1111/bjh.12959] [Citation(s) in RCA: 274] [Impact Index Per Article: 24.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no 'gold standard' test to define deficiency. Serum cobalamin currently remains the first-line test, with additional second-line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first-line test, but an indeterminate 'grey area' may still exist. Plasma homocysteine may be helpful as a second-line test, but is less specific than methylmalonic acid. The availability of these second-line tests is currently limited. Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established. In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment. Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue. Serum folate offers equivalent diagnostic capability to red cell folate and is the first-line test of choice to assess folate status.
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30
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Diagnosis and classification of autoimmune gastritis. Autoimmun Rev 2014; 13:459-62. [DOI: 10.1016/j.autrev.2014.01.048] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 11/13/2013] [Indexed: 12/17/2022]
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31
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Bizzaro N, Antico A. Diagnosis and classification of pernicious anemia. Autoimmun Rev 2014; 13:565-8. [DOI: 10.1016/j.autrev.2014.01.042] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/13/2013] [Indexed: 01/29/2023]
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Abstract
Optimal functioning of the central and peripheral nervous system is dependent on a constant supply of appropriate nutrients. Particularly important for optimal functioning of the nervous system is cobalamin (vitamin B12). Cobalamin deficiency is particularly common in the elderly and after gastric surgery. Many patients with clinically expressed cobalamin deficiency have intrinsic factor-related malabsorption such as that seen in pernicious anemia. The commonly recognized neurological manifestations of cobalamin deficiency include a myelopathy with or without an associated neuropathy. This review deals with neurological aspects of vitamin B12 deficiency and attempts to highlight recent developments.
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Affiliation(s)
- Neeraj Kumar
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
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33
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Takada T, Ikusaka M. [Series: diagnosis at a glance]. ACTA ACUST UNITED AC 2013; 102:3261-3. [PMID: 24605579 DOI: 10.2169/naika.102.3261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Toshihiko Takada
- Department of General Medicine, Chiba University Hospital, Japan
| | - Masatomi Ikusaka
- Department of General Medicine, Chiba University Hospital, Japan
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34
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Izumi K, Fujise T, Inoue K, Mori H, Yamazaki K, Hongou Y, Takagi S, Yamanouchi H, Ashida K, Anzai K. [Mecobalamin improved pernicious anemia in an elderly individual with Hashimoto's disease and diabetes mellitus]. Nihon Ronen Igakkai Zasshi 2013; 50:542-5. [PMID: 24047671 DOI: 10.3143/geriatrics.50.542] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.
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Affiliation(s)
- Kenichi Izumi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Saga Medical School
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35
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15-year-old girl with metaplastic atrophic gastritis and enterochromaffin-like cell hyperplasia. J Pediatr Gastroenterol Nutr 2012; 55:e148-51. [PMID: 22134551 DOI: 10.1097/mpg.0b013e318242da36] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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36
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Suchard MS. Missing: a diagnostic technique to enumerate antigen-specific T cells. Crit Rev Oncol Hematol 2012; 83:276-82. [PMID: 22137827 PMCID: PMC3496851 DOI: 10.1016/j.critrevonc.2011.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2011] [Revised: 10/26/2011] [Accepted: 11/09/2011] [Indexed: 12/14/2022] Open
Abstract
T lymphocytes are responsible for immune responses against pathogens, immune surveillance against cancer and maintenance of tolerance to self. While techniques available to detect antigen-specific T cells have been well described, there is a missing technique in our repertoire. While fluorescent multimers can be used for limited research applications, there is no existing technique suitable for detection of antigen-specific T cells in a diagnostic setting. The absence of such a technology has inhibited the search for "correlates of protection" against infectious, autoimmune or malignant disease. This critical review of existing methods will highlight the limitations of the data on which our current understanding of the immune system is based, in an effort to stimulate development of improved techniques.
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Affiliation(s)
- Melinda Shelley Suchard
- Molecular Medicine and Haematology, National Health Laboratory Service, Faculty of Health Sciences, University of Witwatersrand, 7 York Road Parktown, Johannesburg 2192, South Africa.
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Abstract
Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is the result of intrinsic factor deficiency. Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. Serological markers suggesting the presence of oxyntic mucosa damage are increased levels of fasting gastrin and decreased levels of Pepsinogen I. Without the now obsolete Schilling's test, intrinsic factor deficiency may not be proven, and gastric intrinsic factor output after pentagastric stimulation has been proposed. Intrinsic factor autoantibodies are useful surrogate markers of pernicious anemia. The management of patients with pernicious anemia should focus on the life-long replacement treatment with cobalamin and the monitoring to early diagnose an eventual onset of iron deficiency. Moreover, these patients should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
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Affiliation(s)
- Bruno Annibale
- Department of Digestive and Liver Disease, University Sapienza, Medical School, Ospedale Sant'Andrea, Via di Grottarossa 1035, 00189 Rome, Italy.
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Chan J, Chan HYF. Usefulness of thyrogastric immune features as predictors of pernicious anaemia that lacks intrinsic factor antibody. Int J Lab Hematol 2011; 33:400-8. [PMID: 21251240 DOI: 10.1111/j.1751-553x.2010.01295.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
INTRODUCTION The study aims to evaluate the diagnostic utility of thyrogastric immune features in the identification of intrinsic factor antibody negative (IFA -ve) pernicious anaemia (PA) patients. METHODS Clinico-pathological features of 'intrinsic factor antibody positive (IFA +ve) PA' and 'IFA -ve presumed PA' Chinese patients in a single hospital (2001-2009) were studied. Coefficients of independent variables identified were used as weighted scores. The result was validated by patients (1994-2000) with Schilling test done. RESULTS Comparison of 127 'IFA +ve PA' and 130 'IFA -ve presumed PA' patients showed four independent variables, namely (+) gastric parietal cell (GPC) antibody (OR, 2.907, 95%; CI, 2.346-3.468; P < 0.001), (+) antithyroid antibodies (OR, 3.098, 95%; CI, 2.496-3.70; P < 0.001), (+) gastric atrophy (OR, 3.827, 95%; CI, 3.041-4.64; P = 0.001), and (-) Helicobacter pylori (HP) organisms (OR, 0.134, 95%; CI, -1.60-1.869; P = 0.023). The respective scores were 1.067, 1.131, 1.342 and -2.012. Total scores for each patient ranged from 3.54 to -2.012. When the cut-off score 1.528 was applied to the validation sample (n = 75), the specificity of identifying IFA -ve PA was 100%, sensitivity 53%, positive predictive value 100%, and negative predictive value 36%. CONCLUSION Patients with two out of three features, GPC, antithyroid antibodies, gastric atrophy, but without HP organisms; or three features with HP organisms, can be predicted to have PA.
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Affiliation(s)
- J Chan
- Pamela Youde Nethersole Eastern Hospital, Medicine, Hong Kong, China SAR.
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Lahner E, Spoletini M, Buzzetti R, Corleto VD, Vannella L, Petrone A, Annibale B. HLA-DRB1*03 and DRB1*04 are associated with atrophic gastritis in an Italian population. Dig Liver Dis 2010; 42:854-859. [PMID: 20627832 DOI: 10.1016/j.dld.2010.04.011] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Revised: 02/19/2010] [Accepted: 04/23/2010] [Indexed: 02/08/2023]
Abstract
BACKGROUND Atrophic gastritis (AG) is often considered an autoimmune disorder and is associated with other autoimmune diseases. HLA-DRB1 alleles are often associated with autoimmune diseases, however HLA-DRB1 genotyping data in AG patients are lacking. The objective of the study was to evaluate the prevalence of HLA-DRB1 in AG patients. METHODS The occurrence of HLA-DRB1 alleles was assessed in 89 Italian AG patients (69.1% female) and 313 controls (47.3% females). Genomic DNA was extracted from peripheral venous blood, PCR-coamplified for HLA-DRB1 and typed using a reverse line-blot assay. RESULTS Compared to controls, prevalence of HLA-DRB1*03 (28.1% vs. 15.9%, p=0.01) and HLA-DRB1*04 (25.8% vs. 14.4%, p=0.01) was greater in AG patients, conferring an OR of 2.05 and 2.07, respectively. HLA-DRB1*01 occurred more frequently in controls than in AG patients (11.5% vs. 3.4%, p=0.01) conferring an OR of 0.27. AG patients carrying the HLA-DRB1*03 or *04 alleles were characterised by having more frequently autoimmune thyroid disease (70.4% vs. 42.2%, p=0.01) and intestinal metaplasia (86.4% vs. 62.2%, p=0.01). CONCLUSIONS In our population, over 50% of AG patients carry the HLA-DRB1*03 or *04 alleles associated with autoimmune diseases, suggesting that this subset of AG patients has a genetic predisposition to autoimmunity.
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Affiliation(s)
- Edith Lahner
- Digestive and Liver Disease Unit, 2nd Medical School, Sapienza University, Rome, Italy
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Malizia RW, Baumann BM, Chansky ME, Kirchhoff MA. Ambulatory Dysfunction Due to Unrecognized Pernicious Anemia. J Emerg Med 2010; 38:302-7. [DOI: 10.1016/j.jemermed.2007.05.044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2006] [Revised: 03/05/2007] [Accepted: 05/25/2007] [Indexed: 10/22/2022]
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Abstract
Optimal functioning of the central and peripheral nervous system is dependent on a constant supply of appropriate nutrients. The first section of this review discusses neurologic manifestations related to deficiency of key nutrients such as vitamin B(12), folate, copper, vitamin E, thiamine, and others. The second section addresses neurologic complications related to bariatric surgery. The third sections includes neurologic presentations caused by nutrient deficiencies in the setting of alcoholism. The concluding section addresses neurologic deficiency diseases that have a geographic predilection.
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Affiliation(s)
- Neeraj Kumar
- Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905, USA.
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Schubert ML, D. Kaunitz J. Gastric Secretion. SLEISENGER AND FORDTRAN'S GASTROINTESTINAL AND LIVER DISEASE 2010:817-832.e7. [DOI: 10.1016/b978-1-4160-6189-2.00049-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Lahner E, Annibale B. Pernicious anemia: new insights from a gastroenterological point of view. World J Gastroenterol 2009; 15:5121-5128. [PMID: 19891010 PMCID: PMC2773890 DOI: 10.3748/wjg.15.5121] [Citation(s) in RCA: 174] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2009] [Revised: 09/22/2009] [Accepted: 09/29/2009] [Indexed: 02/06/2023] Open
Abstract
Pernicious anemia (PA) is a macrocytic anemia that is caused by vitamin B(12) deficiency, as a result of intrinsic factor deficiency. PA is associated with atrophic body gastritis (ABG), whose diagnosis is based on histological confirmation of gastric body atrophy. Serological markers that suggest oxyntic mucosa damage are increased fasting gastrin and decreased pepsinogen I. Without performing Schilling's test, intrinsic factor deficiency may not be proven, and intrinsic factor and parietal cell antibodies are useful surrogate markers of PA, with 73% sensitivity and 100% specificity. PA is mainly considered a disease of the elderly, but younger patients represent about 15% of patients. PA patients may seek medical advice due to symptoms related to anemia, such as weakness and asthenia. 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. PA is the end-stage of ABG. Long-standing Helicobacter pylori infection probably plays a role in many patients with PA, in whom the active infectious process has been gradually replaced by an autoimmune disease that terminates in a burned-out infection and the irreversible destruction of the gastric body mucosa. Human leucocyte antigen-DR genotypes suggest a role for genetic susceptibility in PA. PA patients should be managed by cobalamin replacement treatment and monitoring for onset of iron deficiency. Moreover, they should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
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Bermejo F, García-López S. A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases. World J Gastroenterol 2009; 15:4638-43. [PMID: 19787826 PMCID: PMC2754511 DOI: 10.3748/wjg.15.4638] [Citation(s) in RCA: 120] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Iron deficiency (ID), with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by enteroscopy.
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Khan S, Del-Duca C, Fenton E, Holding S, Hirst J, Doré PC, Sewell WAC. Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia. J Clin Pathol 2009; 62:439-41. [PMID: 19398595 DOI: 10.1136/jcp.2008.060509] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific. METHODS The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels. RESULTS Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA. CONCLUSIONS This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.
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Affiliation(s)
- S Khan
- Path Links Immunology, Scunthorpe General Hospital, Scunthorpe, UK.
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Whittingham S, Mackay IR. Autoimmune Gastritis: Historical Antecedents, Outstanding Discoveries, and Unresolved Problems. Int Rev Immunol 2009; 24:1-29. [PMID: 15763987 DOI: 10.1080/08830180590884413] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The earliest recorded history of autoimmune gastritis can be traced to 1849 in London, when Thomas Addison described "a very remarkable form of anemia" later called pernicious (fatal) anemia (PA). This was followed by the recognition of a gastric mucosal defect suspected to have a nutritional basis, the discovery of the megaloblast that characterized the anemia, the insufficiency of a dietary extrinsic factor characterized as vitamin B12 (cobalamin), and a gastric-secreted intrinsic factor. Treatment with vitamin B12 proved curative. The link between PA and gastritis and atrophy was first confirmed histologically after immediate fixation of the stomach postmortem and later, in the 1940s, by peroral tube biopsy. The causes of gastritis remained enigmatic until the era of autoimmunity, when autoantibodies were detected first to gastric intrinsic factor and then to gastric parietal cells. Hints of a dichotomy in pathogenesis of gastritis were crystallized by the description in 1973 of Type A (Autoimmune) and Type B (later, Bacterial) gastritis. Clarification was enhanced by identification in Type A gastritis of the autoantigen of the parietal cell antibody, by the alpha and beta subunits of gastric H+/K+ ATPase, and by the highly informative experimental murine model of postneonatal thymectomy autoimmune gastritis, and in Type B of the causative role of gastric infection with Helicobacter pylori (H. pylori). A denouement will require a full understanding of (1) the origin and pathogenetic contribution of antibody to intrinsic factor; (2) the connection, if any, between H. pylori infection and Type A autoimmune gastritis; and (3) the genetic contributions to gastritis, whether due to autoimmunity or to H. pylori infection.
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Affiliation(s)
- Senga Whittingham
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
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Lahner E, Norman GL, Severi C, Encabo S, Shums Z, Vannella L, Delle Fave G, Annibale B. Reassessment of intrinsic factor and parietal cell autoantibodies in atrophic gastritis with respect to cobalamin deficiency. Am J Gastroenterol 2009; 104:2071-2079. [PMID: 19491828 DOI: 10.1038/ajg.2009.231] [Citation(s) in RCA: 128] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Atrophic body gastritis (ABG) is an autoimmune condition eventually manifesting itself as pernicious anemia (PA). Parietal cell autoantibodies (PCAs) and intrinsic factor autoantibodies (IFAs) are considered characteristics of these conditions. Recent studies on IFA and PCA frequency with respect to cobalamin deficiency in biopsy-proven ABG patients are lacking. We addressed this issue using new enzyme-linked immunosorbent assay (ELISA)-based assays. METHODS Sera from 165 patients with histologically diagnosed ABG and 113 controls were tested for IFA and PCA using ELISA. A total of 81 ABG patients had cobalamin deficiency and macrocytic anemia (Group 1-PA), 36 had cobalamin deficiency without macrocytic anemia (Group 2), and 48 had normal cobalamin levels (Group 3). RESULTS IFAs were detected in 44/165 ABG patients (27% sensitivity) and in 0/113 controls (100% specificity). PCAs were detected in 134 ABG patients (81% sensitivity) and in 11 controls (90% specificity). In Group 1, IFAs showed 37% sensitivity and 100% specificity, whereas PCAs showed 81% sensitivity and 90% specificity. Combining IFA and PCA testing increased the sensitivity to 61% in all ABG patients and to 73% in Group 1, while maintaining 100% specificity. CONCLUSIONS IFAs are 100% specific for biopsy-proven ABG and occurred in 27% of patients. PCAs occurred in 81% of ABG patients and in 10% of controls. Combining IFA and PCA testing significantly increases their diagnostic performance for ABG and PA, yielding a 73% sensitivity for PA. The non-invasive combined PCA and IFA assessment may be useful in selecting patients at risk for autoimmune gastritis to be confirmed by gastroscopic-histologic examination.
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Affiliation(s)
- Edith Lahner
- Department of Digestive and Liver Disease, 2nd Medical School, University Sapienza, Rome 00189, Italy
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Morel S, Georges A, Bordenave L, Corcuff JB. Thyroid and gastric autoimmune diseases. ANNALES D'ENDOCRINOLOGIE 2009; 70:55-8. [DOI: 10.1016/j.ando.2008.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/19/2008] [Revised: 11/18/2008] [Accepted: 11/24/2008] [Indexed: 11/24/2022]
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Abstract
This review describes current knowledge of the main causes of vitamin B12 and folate deficiency. The most common explanations for poor vitamin B12 status are a low dietary intake of the vitamin (i.e., a low intake of animal-source foods) and malabsorption. Although it has long been known that strict vegetarians (vegans) are at risk for vitamin B12 deficiency, evidence now indicates that low intakes of animal-source foods, such as occur in some lacto-ovo vegetarians and many less-industrialized countries, cause vitamin B12 depletion. Malabsorption of the vitamin is most commonly observed as food-bound cobalamin malabsorption due to gastric atrophy in the elderly, and probably as a result of Helicobacter pylori infection. There is growing evidence that gene polymorphisms in transcobalamins affect plasma vitamin B12 concentrations. The primary cause of folate deficiency is low intake of sources rich in the vitamin, such as legumes and green leafy vegetables, and the consumption of these foods may explain why folate status can be adequate in relatively poor populations. Other situations in which the risk of folate deficiency increases include lactation and alcoholism.
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Abstract
Optimal functioning of the central and peripheral nervous system is dependent on appropriate nutrients. Neurologic consequences of nutritional deficiencies are not restricted to underdeveloped countries. Multiple nutritional deficiencies can coexist. Obesity is of particular concern in the developed world. The rising rate of bariatric surgery are accompanied by neurologic complications related to nutrient deficiencies. Prognosis depends on prompt recognition and institution of appropriate therapy. This review discusses peripheral nervous system manifestations related to the deficiency of key nutrients, neurologic complications associated with bariatric surgery, and conditions that have a geographic significance associated with bariatric surgery and certain conditions that have a geographic predilection.
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Affiliation(s)
- Neeraj Kumar
- Department of Neurology, Mayo Clinic, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
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