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Acta Marisiensis - Seria Medica 2023;69(1):61-67 DOI: 10.2478/amma-2023-0012 RESEARCH ARTICLE Clinical characteristics and endoscopic findings in autoimmune gastritis – A retrospective study 1* 2 2 1 1 Gabriella Gabos , Valentin Nădășan , Iris Nădășan , Mădălina Petruț , Ioana Bernatchi , Mădălin 3 1 Bălășescu , Carmen Nicolau 1. Gastroenterology Department, Lotus Image Medical Center Actamedica SRL, Targu Mures, Romania 2. George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania 3. Intensive Care Unit, Mureș County Clinical Hospital, Targu Mures, Romania Objectives: Autoimmune gastritis (AG) is a rare condition that increases the risk of developing stomach adenocarcinomas or carcinoid tu- mours. The objectives of the present research were to summarise the clinical traits of AG patients, together with gastroscopic and histopatho- logic findings, demographic data, and hematologic characteristics. Patients and methods: A medical centre assessed 58 AG patients from January 2019 to December 2022. Results: The majority of the patients were female (73.7%), and the mean age of the participants at the time of the diagnosis was 57.7 ± 12.1 years. We identified pernicious anaemia (54.4%), iron deficiency anaemia (21.1%), as well as autoimmune disorders (96.5%). Though 78.9% of patients reported having gastrointestinal symptoms, 69% presented exclusively upper gastrointestinal symptoms, 17% only had lower, and 14% had concurrent upper and lower gastrointestinal symptoms. All 58 AG patients were exam- ined for associated gastric lesions, although abnormal injuries were detected in only 22 of them. One patient (1.8%) had adenocarcinoma, while five patients (8.8%) had type 1 neuroendocrine tumours (NET). In addition, hyperplastic polyps were found in 16 (28.1%) individuals. Conclusions: Other autoimmune diseases were present with AG, which showed a female predominance. Clinicians should give AG more significant thought by allowing access to interdisciplinary teams. Keywords: autoimmune gastritis, iron/vitamin B12 deficiency, antiparietal cell antibody, multidisciplinary team Received 26 January 2022 / Accepted 2 March 2023 Introduction the clinical symptoms, endoscopic, laboratory, and related Autoimmune gastritis (AG), a form of chronic gastritis, variables in patients with AG for this reason. is caused by the generation of autoantibodies against the proton pump in parietal cells, which destroys the gastric Methods parietal cells . Atrophy and inflammation are limited to the gastric corpus and do not impact the antrum because Patients parietal cells are located in the fundus and corpus glands. Analysis was performed on 58 adult AG patients (>18 The complete destruction of the parietal cells that produce years) diagnosed from January 2019 to December 2022. hydrochloric acid and an intrinsic factor results in perni- The Sydney-Houston pathologic criteria  and the oc - cious anaemia and iron deficiency anaemia. This condition currence of antiparietal cell antibodies (APA) were used to also induces enterochromaffin-like cell hyperplasia and hy - confirm the diagnosis of AG. According to the evalua - pergastrinemia, which result in side effects such as hyper - tion of at least five biopsy fragments taken from the cor - plastic polyps, gastric cancer, or NETs [2-8]. pus (2), the incisura angularis (1), and the more significant Additionally, autoimmune diseases of extra-stomach and lesser curvature of the antrum (2), AG was defined by epithelial tissues like the pancreas or thyroid gland and a the occurence of moderate to severe atrophy of the fun- high prevalence of malignant neoplasms in other organs dus/body with antrum sparing (1). In addition, the de- have been linked to AG [9-13]. Therefore, AG is a gastric mographic information of each patient was also recorded, disorder but should be identified as a systemic disease . including age, gender, family and medical history, associ- In the early stages of the disease, AG is clinically “silent.” ated diseases, age at diagnosis, the presence of concurrent Consequently, the diagnosis of this condition is based only autoimmune disorders, medication history, and symptoms on clinical suspicion . or indications possibly requiring an upper gastrointestinal Early detection is essential because AG can develop iron (UGI) endoscopy. deficiency and/or pernicious anaemia, which are connect - Through a structured interview, we also evaluated the ed to a higher risk of developing gastric pre-malignant and incidence and frequency of gastrointestinal (GI) symptoms malignant conditions [12,13]. Unawareness of this illness at the patient’s initial visit, including heartburn, nausea, may lead to patients being misdiagnosed and, as a result, early satiety, vomiting, regurgitation, postprandial fullness, receiving poor treatment. Our study sought to identify epigastric and abdominal pain, diarrhoea, constipation and bloating. Each participant gave informed consent, and the study * Correspondence to: Gabriella Gabos E-mail: email@example.com received approval from the hospital ethics committee. 62 Acta Marisiensis - Seria Medica 2023;69(1) Laboratory Tests Fischer exact test. Two-tailed p-values were calculated at a After being subjected to overnight fasting, all patients un- significance level of 0.05. derwent a procedure for obtaining a venous blood sample in order to determine serum gastrin, iron, vitamin B , Results APA and anti-H. Pylori IgG levels. Routine laboratory In our investigation, we included a total of 58 patients di- procedures determined regular haematological and bio- agnosed with AG, out of which 42 (73.7%) were women chemical tests. The pattern of anaemia was assessed by and 15 (26.3%) were men; the female-male ratio was 2.8:1. measuring the haemoglobin, mean corpuscular volume At the time of diagnosis, the patient’s mean age was 57.7 ± (MCV), vitamin B12, and ferritin levels. A low haemo- 12.1 years (range 30–80). 4.9% (n=37) of patients reported globin concentration, an MCV > 100 fl, and vitamin B12 moderate coffee intake (1-3 cups/day), while 14.0% (n=8) deficiencies were symptoms of pernicious anaemia that re - of patients reported regular smoking. In addition, 1.8% of sponded to intramuscular B12 vitamin therapy. Low hae- our patients reported drinking on a daily basis (n=1). In moglobin concentration, MCV<80 fl, and ferritin<30 ng/ contrast, 91.2% (n=52) of AG patients did not drink alco- mL were used to define iron deficiency anaemia [15,16]. hol, while 7% (n=4) did so occasionally. Gastrointestinal Plasma gastrin level was determined using the radioimmu- symptoms (group 1, n=45, 78.9%) and anaemia (group 2, noassay with polyethylene glycol, and the presence of APA n=21, 36.8%) were the first triggers for a UGI endoscopy. was determined in serum with an immunofluorescence Hypergastrinemia (4/58, 7%) and neurological symptoms technique. The threshold for an APA positive finding was (1/58, 1%) were additional clues. In 78.9% (n=45) of the 10≥U, and the threshold for a serum gastrin typical result AG patients, there were one or more gastrointestinal prob- was ≤120 pg/mL. Both serologic testing and histological lems. Table I lists the gastrointestinal signs and symptoms examination of H. pylori infection were performed. Pa- that patients were referred to our clinic for. Notably, none tients had not taken proton pump inhibitors (PPIs) for at of these complaints is regarded as indicators of AG. least two months before the examination date. The investi - In the group of symptomatic patients, the majority (n = gation removed five patients having pathologic results con - 40) complained only of upper gastrointestinal symptoms. sistent with AG but APA negative. In contrast, a smaller number (n = 10) complained only of lower gastrointestinal symptoms, while eight patients had Gastroscopic Examinations concurrent upper and lower gastrointestinal symptoms After temporary fasting, a certified endoscopist conducted (Figure 1). endoscopic examinations at our hospital using a FUJIF- UGI endoscopy was performed on all 58 patients. The ILM endoscope, particularly on gastric macroscopic le- results showed varying degrees of mucosal thinness, planed sions. The endoscopist evaluated each patient registered or decreased rugal folds, and submucosal grid vessels in the in this study in order to detect the existence of specific corpus or fundus, whereas the antral mucosa was roughly endoscopic findings such as corpus-dominant atrophy, re - normal. In 28 cases, a sticky, adhesive mucous that was moval of the gastric folds, sticky adherent dense mucus and firmly adhered to the mucosa of the fundus did not re - remnant oxyntic mucosa; moreover, the investigation was semble the milky, clouded mucous formed by H. pylori meant to highlight other comprehensive results like cancer, infection. NET, adenoma, and hyperplastic polyps. Findings were Related gastric lesions were assessed in all 58 patients, concordant to the global impression of the particularity of and 22 presented abnormal lesions. One patient (1.8%) any macroscopic lesion. Polypoid lesions were categorized had adenocarcinoma, while five patients (8.8%) had type 1 macroscopically in accordance with Kudo’s Classification NET. In 16/58 (28.1%) patients, hyperplastic polyps were . When the corpus and fundus showed more evidence found. The median diameter of type I NETs was 5 mm of gastric mucosal atrophy than the antral region, as was (range 1–25 mm). All NETs situated in the gastric fundus predicted based on visible submucosal vessels in endoscop- Table I. Frequency and percentage of gastrointestinal symptoms in ic appearances, those cases were recorded as suspected AG. the 58 patients of AG N % Symptoms Statistical Analysis Epigastric pain 35 61,4 Descriptive statistics included computing means and Abdominal pain 21 36,8 standard deviations (SD) for numeric variables and abso- Bloating 18 31,6 lute and relative frequencies (%) for categorical variables. Acid regurgitation 16 28,1 Comparisons were performed between (a) patients with Heartburn 16 28,1 gastrointestinal symptoms vs anaemia, and (b) patients Vomiting 10 17,5 with vs without HPA. We used the Kolmogorov-Smirnov Nausea 8 14,0 test to determine normality of data. Furthermore, to com- Constipation 6 10,5 pare numerical data with normal and non-normal distri- Diarrhea 5 8,8 bution the Student’s t-test and Mann-Whitney test were Weight loss 5 8,8 used. In order to compare categorical data we used the Acta Marisiensis - Seria Medica 2023;69(1) 63 One patients had adenocarcinoma. The endoscopic pic - ture shows an irregular depressed tumor in the posterior wall of the gastric corpus (Figure 4). Pronounced vascu- lar visibility and the disappearance of folds are detected in the lesser curvature of the corpus. Biopsies from the lesion showed gastric adenocarcinoma (Figure 5). The patient un- derwent total gastrectomy. Gastric hyperplastic polyps were found at endoscopy in 16 patients (six solitary, ten multiple) (Figure 6). Polyps were situated in the antrum alone in six patients, in the body and fundus in 10. Polyps of the body and fundus were mostly mutiple, while solitary polyps were more fre- quent in the antrum. Only five polyps were larger than 1cm in diameter, the greatest being 1.5 cm. Biopsies were Fig. 1. Distribution of patients based on the type of reported gas- taken from the surface of the polyps in 16 patients; and trointestinal symptoms they proved to be hyperplastic on histology (Figure 7). En- doscopic polypectomy was performed. and corpus, morphological characteristic shows principally In AG patients under 40, no gastric endoscopic lesions protruding polypoid lesions (Figure 2). Central depression were discovered; each patient who presented gastric le- of the lesion appeared in 3 cases. The color tone was gen - sions was older than 40. The incidence of gastric lesions erally light yellow or red or was the same color as the sur- was also unrelated to H. pylori (p = 1.0), iron deficiency rounding mucosa. Type I NETs was treated via endoscopic (p = 0.9086), gender (p = 0.3709), accompanying autoim- resection in all five patients. The histopathological imaging mune illnesses (p = 0.7758), and smoking (p = 0.4657). of type I NET shows proliferation of neuroendocrine cells B12 levels were considerably lower in patients with gas- arranged in nests, cors or trabecules. The cells are bland, tric lesions than those without (140.8 pg/ml and 259.2 round to oval with typical salt amd pepper chromatin and pg/ml, respectively; p = 0.0318). In patients with lesions, amphophilic cytoplasm (Figure 3). serum gastrin levels were substantially higher (611.7 pg/ Fig. 2. Endoscopic images of type I gastric NETs with a background of atrophic gastritis. The endoscopic picture shows polypoid lesions in the greater curvature of the corpus with the disappearance of folds. The tumor is gently elevated. Fig. 3. Histopatological imaging of type I NET 64 Acta Marisiensis - Seria Medica 2023;69(1) Fig. 7. Elongated, branching, and dilated hyperplastic foveolae ly- ing in an edematous, hypervascular, inflammatory stroma Fig. 4. Endoscopic images in gastric cancer patients with AG ml vs. 369.5 pg/ml; p = 0.0103). Patients in group 1 had more gastric endoscopic lesions than patients in group 2, according to research (p=0.4682). All of the patients had hypergastrinemia (mean, 462.9352.9 pg/mL; range, 122- 2133 pg/mL), 100% of the serum APA tests were positive (58/58), and the average levels of blood B12 and iron were 66.639.2 ug/dl and 214.6185.5 pg/mL, respectively. Based on MCV, patients were distributed as follows: 24 patients presented an MCV > 100 fl, 4 had an MVC < 80 fl, while 26 had normocytic (MCV 82.9–98 fl) indices. Twenty-one cases (36.8%) were found to have anaemia, of which 12 (21.1%) had iron deficiency anaemia, and 30 (54.4%) had megaloblastic anaemia. Average folic acid levels were pre- sent in each subject. The histological examination revealed no evidence of H. pylori infection in any of the patients. However, a serologic test showed that 16 patients (28.1%) were positive for H. pylori. Fewer patients in group 2 tested positive for H. pylori by serology than in group 1 (3 vs 9). Nevertheless, the difference did not meet statistical signifi - cance (p=1). 56 of the 58 patients had other autoimmune illnesses at the same time. The most prevalent condition was chronic autoimmune thyroiditis (23 of 58; 41.1%), which was followed by alopecia (1 of 58; 19.3%), rheumatoid ar- thritis (8 of 58; 14%), vitiligo (6 of 58; 10.5%), psoriasis (5 of 58; 8.8%), and type I diabetes mellitus (3 of 58; 5.3%). In 40% of patients with joint disorders such as diabe- tes, osteoporosis, cardiovascular diseases, and dyslipidemia, Fig. 5. Neoplastic tubules or intestinal glands resembling colonic polypharmacy (the use of more than two medicines) was adenocarcinoma, may contain apical mucin vacuoles prevalent. Approximately 20% of patients took prokinet- ics. Serum gastrin levels significantly differed between group 1 — patients with abdominal symptoms — and group 2 — patients with iron/B12 deficiencies (Table II). Sixteen (28.1%) patients tested positive for anti-H. Py lori IgG. Patients with and without H. pylori did not differ in terms of gender, age, smoking habits, serum gastrin, or vitamin B12. (Table III) Discussion The development of chronic, ongoing inflammation and gastric mucosal atrophy in the body and fundus of the Fig. 6. Enoscopic image of hyperplastic polip Acta Marisiensis - Seria Medica 2023;69(1) 65 Table II. Demographic, laboratory and clinical features and comparison of these parameters according to the symptom groups. Group 1- abdominal symptoms Group 2 - iron/B12 deficiency p Age (years); mean (SD) 58.2 (11.9) 63.2 (12.3) 0.2065 Sex; n (%) Female 29 (82.9) 6 (17.1) 0.1399 Male 8 (61.5) 5 (38.5) Smoking; n (%) Non-smoker 30 (73.2) 11 (26.8) 0.1791 Smoker 7 (100.0) 0 (0.0) Anti-H. pylori IgG; n (%) Yes 9 (75%) 3 (25.0) 1.0 No 28 (77.8) 8 (22.2) APA (U/ml); medie (SD) 57.7 (33.5) 65.7 (24.3) 0.4654 Gastrin (pg/ml); mean (SD) 388.9 (280.2) 711.8 (538.1) 0.0133 B12 (pg/ml); mean (SD) 257.7 (201.5) 141.2 (119.1) 0.1162 a: Mann-Whitney test; b: Fischer exact test; c: student t test stomach is caused by AG, which is created by cellular and , while the prevalence of iron deficiency anaemia in humoral immune reactions against gastric parietal cells our group (13.7%, 8/58) is consistent with the most recent [1,18,19]. Anacidity, iron deficiency anaemia and perni - report . cious anaemia are apparent in affected patients as the con - Other autoimmune diseases, such as thyroid conditions dition progresses [20,21]. The prevalence of AG varies de - or alopecia, were usually present in 56 out of 58 (98.5%) pending on the criteria utilized, and no definitive criteria patients, a result highlighted in earlier publications [28, for diagnosis have been recognized . The prevalence 29]. Therefore, even though gastric NETs and stomach has also been noted to differ amongst various populations cancer are frequently believed to be the side effects of AG, and groups [18,19]. The primary diagnostic criteria for this it is imperative to thoroughly take into account the conse- condition are mucosal atrophy and inflammation brought quences of other autoimmune diseases at the time of diag- on by the immune system’s response to parietal cells. nosis and during follow-up . Our group exhibited a much larger percentage of fe- Our data evidenced no ongoing H. pylori infection in male patients with AG, in line with studies on Western patients included in the present study; still, anti-H. Pylori and Asian [23,24] populations demonstrating a higher fre- IgG was positive in 16 (28.1%) of them. Gender, age, quency of AG in females and the elderly (73.3%). smoking habits, vitamin B12 and serum gastrin levels The most frequent reasons for people to seek medical did not differ between H. pylori-positive and H. pylori- care are gastrointestinal symptoms and an iron/vitamin negative individuals. When examined with serology and B12 deficiency. Purdy et al. investigated 56 patients histology, two-thirds of patients who presented atrophic highlighting similar results with our findings. Thus, 74% corpus gastritis confirmed H. pylori infection, according of their patients were female, with a median age of 62 and to Annibale et al.  In a similar study, the same re- most of their symptoms (29%) were pain related. In our searchers identified that H. pylori serology was positive in study, pain was related to abdominal bloating. Most symp- 62% of patients who presented atrophic corpus gastritis tomatic AG patients (about 70%) reported upper gastro- and pernicious anaemia . Nevertheless, according to intestinal problems. One-fourth of the reported upper gas- Mini et al.  among the 111 patients with atrophic trointestinal symptoms were GERD-related, whether the corpus gastritis with negative H. pylori serology 95.5% condition was remote or in conjunction with dyspepsia. presented positive immunoblotting. Unfortunately, we The incidence of pernicious anaemia in our sample lacked the necessary conditions to use this method to (43.1%, 25/58) is consistent with earlier publications research our patients. Subsequently, bacterial contamina- Table III. Association between clinical and laboratory parameters and H.pylori status Serologic H.pylori positive AG patients Serologic H.pylori negative AG patients p Age (years); mean (SD) 58.0 (12.7) 60.6 (11.6) 0.4674 a Sex; n (%) Female 14 (33.3) 28 (66.7) 0.1896 b Male 2 (13.3) 13 (86.7) Smoking; n (%) Non-smoker 14 (28.6) 35 (71.4) 1.0 b Smoker 2 (25.0) 6 (75.0) Gastrin (pg/ml); mean (SD) 340.4 (206.3) 507.2 (391.3) 0.1081 c B12 (pg/ml); mean (SD) 160.9 (159.6) 232.7 (192.3) 0.0639 c a: Student t test; b: Fischer exact test; c: Mann-Whitney test 66 Acta Marisiensis - Seria Medica 2023;69(1) tion may be an essential autoimmune process in the ad- establish a specialised multidisciplinary team (pathologists, vancement of AG. gastroenterologists, endocrinologists, immunologists, hae- AG is characterised by progressive corpus dominant matologists, and surgeons) to thoroughly assess patients mucosal atrophy, pale mucosa with clear submucosal vas- with AG. cular visibility and non-atrophic mucosa in the antrum. The current study contains several drawbacks. Firstly, it Additional endoscopic features comprise remnant oxyntic was a retrospective study that took place in a single centre. mucosa and viscous adherent thick mucus . AG can Secondly, the levels of anti-intrinsic factor antibodies were lead to neoplastic transformations as a chronic inflamma - not determined; the diagnosis of AG was restricted to en- tory illness, such as gastric adenoma or adenocarcinoma doscopically reported atrophy and serological APA levels. [6,35]. One of the typical concomitant gastric lesions of To better comprehend the aspects of this condition, a more AG is type 1 NET. Type 1 NET is defined as having a vari - thorough, comprehensive investigation is required. able prevalence in AG. According to a study, NET preva- lence in AG ranged from 5.2% to 11% . A histological Acknowledgements review conducted in the USA  revealed a prevalence of This work was supported by a grant of Ministry of Re - NET of 9.97%, whereas a Chinese study  revealed a search and Innovation-project number ID P_34_498, prevalence of 4.37%. Our analysis discovered a prevalence within MFE 2014-2020-POC. of 8.6% (5/58) consistent with other results. Endoscopic lesions in 461 individuals with AG were Authors’ contribution evaluated by Park et al. . They came to the conclusion GG – significant contributions to conception and design, that individuals with AG are much more likely to acquire systematic literature research, choosing studies to include, polyps and neoplasms since 143 of these patients had 240 data analysis and interpretation, writing the article and gastric endoscopic lesions (179 polyps, 46 gastric carci- critically reviewing it for significant intellectual content, noids, 11 adenocarcinomas, 3 lymphomas, and 1 gastro- and final consent of the version that will be published. intestinal stromal tumour (GIST). We identified gastric VN - analysis and interpretation of the data, writing and lesions in 22 (37.9%) of our patients (type I NET in 5, critically editing the research for main intellectual content, adenocarcinoma in 1, and hyperplastic polyps in 16 pa- and final publishing consent. tients). In this research, all the patients diagnosed with gas- IN- analyzing and interpreting data, writing, and critically tric lesions were older than 40 and had significantly lower editing the research paper for important intellectual con- B12 levels and higher serum gastrin levels (p = 0.0103) tent, and final publishing consent than those without lesions (p = 0.0318). MP - data interpretation, critical revision for meaningful Consistent endoscopic surveillance of AG patients is es- intellectual content, and final publishing consent sential to detect concurrent gastric neoplasms early. Un- IB - data interpretation, critical revision for significant in - fortunately, especially in the early stages, diagnostic delays tellectual content, and final consent of the version that will happen frequently, given the indolent progress and usually be published quiet clinical appearance of the disease. Therefore, clini - MB - data interpretation, critical revision for substantial cians should be knowledgeable about the best diagnosis intellectual content, and final consent of the version that and treatment techniques to lower the risk of unfavourable will be published outcomes. Our research, we think, will make possible AG CN- data interpretation, critical revision for important in- diagnosis simpler. According to our data, most AG patients tellectual content, and final consent of the version that will were female, and comorbidity with other autoimmune dis- be published eases was relatively common. Although this group’s clinical manifestations varied, most patients sought medical atten- Conflict of interest tion for symptoms associated with abdominal bloating and None to declare. iron and/or vitamin B12 deficiencies. The heterogenity of this condition’s clinical signs should be known to doctors. References 1. Strickland RG, Mackar IR. 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Acta Marisiensis - Seria Medica – de Gruyter
Published: Mar 1, 2023
Keywords: autoimmune gastritis; iron/vitamin B12 deficiency; antiparietal cell antibody; multidisciplinary team
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