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Gastroenterology Oct 2021The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common... (Review)
Review
DESCRIPTION
The purpose of this Clinical Practice Update Expert Review is to provide clinicians with guidance on the diagnosis and management of atrophic gastritis, a common preneoplastic condition of the stomach, with a primary focus on atrophic gastritis due to chronic Helicobacter pylori infection-the most common etiology-or due to autoimmunity. To date, clinical guidance for best practices related to the diagnosis and management of atrophic gastritis remains very limited in the United States, which leads to poor recognition of this preneoplastic condition and suboptimal risk stratification. In addition, there is heterogeneity in the definitions of atrophic gastritis, autoimmune gastritis, pernicious anemia, and gastric neoplasia in the literature, which has led to confusion in clinical practice and research. Accordingly, the primary objective of this Clinical Practice Update is to provide clinicians with a framework for the diagnosis and management of atrophic gastritis. By focusing on atrophic gastritis, this Clinical Practice Update is intended to complement the 2020 American Gastroenterological Association Institute guidelines on the management of gastric intestinal metaplasia. These recent guidelines did not specifically discuss the diagnosis and management of atrophic gastritis. Providers should recognize, however, that a diagnosis of intestinal metaplasia on gastric histopathology implies the diagnosis of atrophic gastritis because intestinal metaplasia occurs in underlying atrophic mucosa, although this is often not distinctly noted on histopathologic reports. Nevertheless, atrophic gastritis represents an important stage with distinct histopathologic alterations in the multistep cascade of gastric cancer pathogenesis.
METHODS
The Best Practice Advice statements presented herein were developed from a combination of available evidence from published literature and consensus-based expert opinion. No formal rating of the strength or quality of the evidence was carried out. These statements are meant to provide practical advice to clinicians practicing in the United States. Best Practice Advice Statements BEST PRACTICE ADVICE 1: Atrophic gastritis is defined as the loss of gastric glands, with or without metaplasia, in the setting of chronic inflammation mainly due to Helicobacter pylori infection or autoimmunity. Regardless of the etiology, the diagnosis of atrophic gastritis should be confirmed by histopathology. BEST PRACTICE ADVICE 2: Providers should be aware that the presence of intestinal metaplasia on gastric histology almost invariably implies the diagnosis of atrophic gastritis. There should be a coordinated effort between gastroenterologists and pathologists to improve the consistency of documenting the extent and severity of atrophic gastritis, particularly if marked atrophy is present. BEST PRACTICE ADVICE 3: Providers should recognize typical endoscopic features of atrophic gastritis, which include pale appearance of gastric mucosa, increased visibility of vasculature due to thinning of the gastric mucosa, and loss of gastric folds, and, if with concomitant intestinal metaplasia, light blue crests and white opaque fields. Because these mucosal changes are often subtle, techniques to optimize evaluation of the gastric mucosa should be performed. BEST PRACTICE ADVICE 4: When endoscopic features of atrophic gastritis are present, providers should assess the extent endoscopically. Providers should obtain biopsies from the suspected atrophic/metaplastic areas for histopathological confirmation and risk stratification; at a minimum, biopsies from the body and antrum/incisura should be obtained and placed in separately labeled jars. Targeted biopsies should additionally be obtained from any other mucosal abnormalities. BEST PRACTICE ADVICE 5: In patients with histology compatible with autoimmune gastritis, providers should consider checking antiparietal cell antibodies and anti-intrinsic factor antibodies to assist with the diagnosis. Providers should also evaluate for anemia due to vitamin B-12 and iron deficiencies. BEST PRACTICE ADVICE 6: All individuals with atrophic gastritis should be assessed for H pylori infection. If positive, treatment of H pylori should be administered and successful eradication should be confirmed using nonserological testing modalities. BEST PRACTICE ADVICE 7: The optimal endoscopic surveillance interval for patients with atrophic gastritis is not well-defined and should be decided based on individual risk assessment and shared decision making. A surveillance endoscopy every 3 years should be considered in individuals with advanced atrophic gastritis, defined based on anatomic extent and histologic grade. BEST PRACTICE ADVICE 8: The optimal surveillance interval for individuals with autoimmune gastritis is unclear. Interval endoscopic surveillance should be considered based on individualized assessment and shared decision making. BEST PRACTICE ADVICE 9: Providers should recognize pernicious anemia as a late-stage manifestation of autoimmune gastritis that is characterized by vitamin B-12 deficiency and macrocytic anemia. Patients with a new diagnosis of pernicious anemia who have not had a recent endoscopy should undergo endoscopy with topographical biopsies to confirm corpus-predominant atrophic gastritis for risk stratification and to rule out prevalent gastric neoplasia, including neuroendocrine tumors. BEST PRACTICE ADVICE 10: Individuals with autoimmune gastritis should be screened for type 1 gastric neuroendocrine tumors with upper endoscopy. Small neuroendocrine tumors should be removed endoscopically, followed by surveillance endoscopy every 1-2 years, depending on the burden of neuroendocrine tumors. BEST PRACTICE ADVICE 11: Providers should evaluate for iron and vitamin B-12 deficiencies in patients with atrophic gastritis irrespective of etiology, especially if corpus-predominant. Likewise, in patients with unexplained iron or vitamin B-12 deficiency, atrophic gastritis should be considered in the differential diagnosis and appropriate diagnostic evaluation pursued. BEST PRACTICE ADVICE 12: In patients with autoimmune gastritis, providers should recognize that concomitant autoimmune disorders, particularly autoimmune thyroid disease, are common. Screening for autoimmune thyroid disease should be performed.
Topics: Benchmarking; Clinical Decision-Making; Consensus; Diagnostic Techniques, Digestive System; Gastritis, Atrophic; Gastroenterology; Humans; Predictive Value of Tests; Treatment Outcome
PubMed: 34454714
DOI: 10.1053/j.gastro.2021.06.078 -
Journal of Evidence-based Medicine May 2021Pernicious 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... (Review)
Review
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.
Topics: Anemia, Pernicious; Humans; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 34015185
DOI: 10.1111/jebm.12435 -
Lancet (London, England) Jun 2023A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over...
Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.
BACKGROUND
A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases.
METHODS
In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex.
FINDINGS
Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases.
INTERPRETATION
Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases.
FUNDING
Research Foundation Flanders.
Topics: Humans; Male; Female; Child; Middle Aged; Incidence; Sjogren's Syndrome; Cohort Studies; Diabetes Mellitus, Type 1; Prevalence; Anemia, Pernicious; Celiac Disease; Autoimmune Diseases; Social Class; Graves Disease; Lupus Erythematosus, Systemic; England; Thyroiditis
PubMed: 37156255
DOI: 10.1016/S0140-6736(23)00457-9 -
Archives of Pathology & Laboratory... Nov 2019Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia.... (Review)
Review
CONTEXT.—
Autoimmune gastritis (AG) is a corpus-restricted chronic atrophic gastritis associated with intrinsic factor deficiency, either with or without pernicious anemia. Autoimmune gastritis is a microscopic disease because patients present with no or vague symptoms, and clinicians rarely find endoscopic changes. Autoimmune gastritis only becomes a clinical disease when pathologists diagnose it in gastric biopsies performed for a variety of clinical indications. Unfamiliarity with this disease can result in misdiagnosis of patients, and thus inadequate patient management.
OBJECTIVE.—
To review the pathogenesis, clinical features, diagnostic criteria, differential diagnoses, sequelae, and surveillance recommendations for AG.
DATA SOURCES.—
The sources of the study include a review of the pertinent literature for AG.
CONCLUSIONS.—
Autoimmune gastritis is an important disease characterized by a loss of oxyntic mucosa and presence of metaplastic epithelium and enterochromaffin-like cell hyperplasia. Awareness and proper diagnosis are critical to prevent mismanagement of patients.
Topics: Anemia, Pernicious; Autoimmune Diseases; Biopsy; Chronic Disease; Diagnosis, Differential; Diagnostic Errors; Epithelium; Gastritis, Atrophic; Humans; Hyperplasia; Intrinsic Factor; Metaplasia; Stomach
PubMed: 31661309
DOI: 10.5858/arpa.2019-0345-RA -
Vitamins and Hormones 2022Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC)... (Review)
Review
Vitamin B12 is assimilated and transported by complex mechanisms that involve three transport proteins, intrinsic factor (IF), haptocorrin (HC) and transcobalamin (TC) and their respective membrane receptors. Vitamin deficiency is mainly due to inadequate dietary intake in vegans, and B12 malabsorption is related to digestive diseases. This review explores the physiology of vitamin B12 absorption and the mechanisms and diseases that produce malabsorption. In the stomach, B12 is released from food carrier proteins and binds to HC. The degradation of HC by pancreatic proteases and the pH change trigger the transfer of B12 to IF in the duodenum. Cubilin and amnionless are the two components of the receptor that mediates the uptake of B12 in the distal ileum. Part of liver B12 is excreted in bile, and undergoes an enterohepatic circulation. The main causes of B12 malabsorption include inherited disorders (Intrinsic factor deficiency, Imerslund-Gräsbeck disease, Addison's pernicious anemia, obesity, bariatric surgery and gastrectomies. Other causes include pancreatic insufficiency, obstructive Jaundice, tropical sprue and celiac disease, bacterial overgrowth, parasitic infestations, Zollinger-Ellison syndrome, inflammatory bowel diseases, chronic radiation enteritis of the distal ileum and short bowel. The assessment of B12 deficit is recommended in the follow-up of subjects with bariatric surgery. The genetic causes of B12 malabsorption are probably underestimated in adult cases with B12 deficit. Despite its high prevalence in the general population and in the elderly, B12 malabsorption cannot be anymore assessed by the Schilling test, pointing out the urgent need for an equivalent reliable test.
Topics: Adult; Aged; Anemia, Megaloblastic; Humans; Intrinsic Factor; Malabsorption Syndromes; Male; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 35337622
DOI: 10.1016/bs.vh.2022.01.016 -
Muscle & Nerve Jul 2020Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns,... (Review)
Review
Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.
Topics: Anemia, Pernicious; Avitaminosis; Dietary Supplements; Humans; Nutritional Status; Peripheral Nervous System Diseases; Thiamine Deficiency; Vitamin B 12 Deficiency; Vitamins
PubMed: 31837157
DOI: 10.1002/mus.26783 -
Blood May 2020
Topics: Adult; Anemia, Pernicious; Female; Humans; Prognosis; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B Complex
PubMed: 32379881
DOI: 10.1182/blood.2020005344 -
Nutrients Apr 2022Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from... (Review)
Review
Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.
Topics: Anemia, Pernicious; Gastritis; Humans; Micronutrients; Precancerous Conditions; Stomach Neoplasms; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 35458234
DOI: 10.3390/nu14081672 -
Nature Reviews. Disease Primers Jul 2020Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to... (Review)
Review
Autoimmune gastritis (AIG) is an increasingly prevalent, organ-specific, immune-mediated disorder characterized by the destruction of gastric parietal cells, leading to the loss of intrinsic factor and reduced acid output. These alterations result in malabsorption of iron, vitamin B (pernicious anaemia) and potentially other micronutrients. For several years, most studies have focused on pernicious anaemia only, generating confusion between the two entities. In AIG, the gastric proton pump, H/K ATPase, is the major autoantigen recognized by autoreactive T cells. The T cell-dependent activation of B cells stimulates the production of anti-parietal cell antibodies, the serological hallmark of AIG. The role of Helicobacter pylori infection in activating or favouring the autoimmune process is still uncertain. Early histopathological alterations allowing a more precise and prompt recognition have recently been described. AIG is burdened by a substantial diagnostic delay as it can present with varied clinical signs including, among others, gastrointestinal symptoms and neuropsychiatric manifestations. In advanced stages, AIG might progress to neuroendocrine tumours and gastric adenocarcinoma. Management includes early detection through a proactive case-finding strategy, micronutrient supplementation and endoscopic surveillance. This Primer comprehensively describes the most important insights regarding the epidemiology, pathophysiology, diagnosis and management of AIG, focusing on the most controversial, outstanding issues and future directions.
Topics: Disease Management; Graves Disease; Humans; Receptors, Thyrotropin
PubMed: 32647173
DOI: 10.1038/s41572-020-0187-8