자가면역성위염 환자에서 자가면역성 갑상선 질환 동반 가능성이 높고, 그 반대의 경우도 중요합니다. 자가면역성 갑상선 질환 중 하나인 그레이브씨병 치료 후 생긴 갑상선기능저하로 약물치료 중인 환자에서 시행한 혈청학적 검사에서 자가면역성위염이 의심되어 내시경 검사를 통해 진단 된 환자에 대하여 연구회에서 직접 작성한 case report 입니다. 향후, Case control study가 필요할 것 같습니다.
Patient with Graves’ disease suspected with autoimmune gastritis before endoscopy
Abstract
Autoimmune gastritis (AIG) is a representative disease of atrophic gastritis caused by destruction of parietal cell in the fundus and body of stomach as a result of a chronic inflammatory responses through an immune reaction. Since it is characterized by extensive atrophy of the body, endoscopic findings are an important clue in diagnosis. Diagnosis is made through serological and histological tests based on endoscopic findings, but it can be accompanied by autoimmune diseases such as autoimmune thyroid diseases (ATD), and vice-versa can be suspected. In addition, AIG often does not have clear clinical symptoms, and diagnosis is likely to be delayed because it is difficult to suspect before symptoms due to accompanying diseases. We report in a patient with Graves’ disease, one of the ATD, severe serological atrophy, hypergastrinemia, and anti-parietal cell antibody positive was suspected through serological tests, and then diagnosed through endoscopy and biopsy.
Key words: Autoimmune disease; Gastritis; Graves’ disease; Gastrin
Introduction
The intestine, stomach, and thyroid gland develop from the same origin at the embryonic stage; thus, autoimmune thyroid diseases (ATD) such as Hashimoto’s thyroiditis and Graves’ disease, which can be accompanied by autoimmune gastritis (AIG) or celiac disease, were previously known as “thyro-gastric syndrome.”1,2) AIG is an immune-mediated disease with consistant inflammatory responses occurring through auto-activated T cells caused by reacting with antibodies that recognize the H+/K+ ATPase in parietal cells secreting gastric acid which leads gastric corpus atrophy.3) The gradual parietal cell destruction subsequently leads to a remarkable decline in gastric acid and intrinsic factor secretions, thereby resulting in iron, vitamin B12, and micronutrient deficiencies, with a possibility of anemia, sensory and peripheral neuropathy, infertility, and repeated miscarriages.4) Owing to extensive histopathologic evolution of gastric corpus atrophy, injured chief cells and increased gastrin cell expressions exhibit a notable decline in serum pepsinogen I and pepsinogen I/II ratio and an elevated gastrin in the blood through a serum test, which are characteristics of serological atrophic gastritis.3-5) However, AIG does not present with distinct clinical signs and typically occurs asymptomatically, and then the final diagnosis is delayed owing to misdiagnose it as functional dyspepsia, gastroesophageal reflux disease, or anemia.6) The standard diagnosis method of AIG is to perform an endoscopy and biopsy to determine inflammatory conditions in the gastric corpus, whereas a serum test and a positive anti-parietal cell antibody test preferentially could be performed if an autoimmune disease (AD) is suspected highly accompanied by AIG.7) This is a case report of a patient with Graves’ disease, confirmed to have a positive anti-parietal cell antibody and severe serological atrophy based on a serum test to identify the occurrence of AIG, and then an endoscopy was performed to make a histological diagnosis.
Case report
A 44-year-old woman diagnosed with Graves’ disease approximately 8 years before the study period was treated with radioactive iodine. Therefore, she developed hypothyroidism and was consequently consuming 0.1 mg of synthyroid. The patient underwent a blood transfusion owing to severe iron-deficiency anemia during pregnancy and was intermittently taking iron supplements. She had no gastrointestinal symptoms and has not taken gastric acid secretion inhibitors or receiving treatment for Helicobacter pylori (H. pylori).
A blood test was performed to assess anemia and thyroid levels, showing the following results: hemoglobin, 7.5 (reference range, 12.0–16.0) g/dL; hematocrit, 25.1% (37.0–40.0%); mean corpuscular volume (MCV), 73.2 (80.0–100.0) Fl; mean corpuscular hemoglobin (MCH), 21.6 (27.0–34.0) pg; MCH concentration, 29.5 (32.0–36.0) g/dL; Fe, 13 (33–193) μg/dL; ferritin, 8.10 (13.0–150.0) ng/mL; transferrin and iron-binding capacity, 371 (228–428) μg/dL; and vitamin B12, 403 (180–914) pg/mL; thus, it was diagnosed as iron-deficiency anemia. Furthermore, the results presented free T4 of 1.32 (reference range, 0.85–1.50) ng/dL; T3, 1.62 (0.58–1.62) ng/mL; thyroid stimulating hormone (TSH), <0.05 (0.25–5.00); TSH receptor antibody, 2.26 (0.0–1.22) IU/L; anti-thyroid-peroxidase antibody, 10.1 (0.0–34.0) IU/mL; and thyroglobulin antibody, 13.9 (0.0–115.0) IU/mL, indicating that the thyroid gland function was well maintained after a radioactive iodine treatment. Although no distinct gastrointestinal symptom was observed, thus a serum test was performed to determine the occurrence of accompanying AIG. The results demonstrated pepsinogen I, II, and I/II ratio was 28.7 ng/mL, 26.3 ng/mL, and 1.1, respectively, presenting very low pepsinogen I level and pepsinogen I/II ratio and elevated serum gastrin level to 792 (13–115) pg/mL. Anti-H. pylori antibodies were measured using H. pylori IgG Immulite® 2000 (Siemens, USA), presenting a positive result of 4.27 U/mL (negative, <0.90 U/mL; equivocal, 0.90–1.09 U/mL; positive, ≥1.10 U/mL). Additionally, an anti-parietal cell antibody test using immunofluorescence assay (KALLESTAD Mouse Stomach/Kidney, Bio RAD, USA) revealed positive results; thus, autoimmune hyperthyroidism accompanied by AIG was suspected.
Endoscopy to diagnose AIG and identify the presence of accompanying H. pylori infection revealed mild atrophy in the gastric antrum (Fig. 1A). However, submucosal blood vessels were markedly observed in the gastric fundus and body, showing corpus-dominant atrophy with gastric-fold disappearance (Fig. 1B). Spotty redness caused by H. pylori was observed in the greater curvature of the gastric body (Fig. 1C). Therefore, the rapid urease test was performed, which was confirmed to be positive. Biopsies were obtained from the gastric antrum and body, respectively. Results showed some atrophic changes and inflammatory cell infiltration in the mucosa of the gastric antrum (Fig. 2A), whereas atrophy was considerably severe in the mucosa at the greater and lesser curvatures of the gastric body, and inflammatory cell infiltration was distinct in the lamina propria (Fig. 2B). The immunohistochemistry results using chromogranin revealed proliferation of enterochromaffin-like cells in the gastric body (Fig. 2C). The patient was eventually diagnosed with AIG and started to take iron supplements and is receiving outpatient follow-up care after being prescribed medications for H. pylori eradication.
Discussion
ATD are accompanied with AIG in 35% of patients, and anti-parietal cell antibodies are most commonly accompanied with organ-specific autoantibodies.8,9) More than half of the patients with AIG may develop AD, and ATD are the most common comorbidity in approximately >36% of patients.10) Graves’ disease is the most common type of ATD and is accompanied by anemia in >30%.11,12) Regarding the anemia pattern, the chronic disease-like “Graves’ anemia” is the most common, which maintains normal thyroid levels post-treatment and improves in most cases.12) In this patient, no medical record was reviewed before radioactive iodine treatment for Graves’ disease; thus, whether there was Graves’ anemia or not remains unclear. However, considering that normal thyroid levels were maintained post-treatment and a markedly reduced MCV and ferritin level was observed, anemia at the time of hospital visit was diagnosed as iron-deficiency anemia rather than Graves’ anemia. When Graves’ disease is accompanied by iron-deficiency anemia, the expression of anti-parietal antibodies is increased in many cases, which are characteristics of AIG, as well as elevated serum gastrin.13) The proliferation of enterochromaffin-like cells can be observed, which may progress to neuroendocrine tumors in patients with ATD associated with AIG, and in such histological changes, the elevated serum gastrin is diagnostically significant.10,12-14) Furthermore, in patients with ATD, a serum pepsinogen test can be used as an important biomarker that confirms severe histological atrophy, irrespective of H. pylori infection.15) Severe atrophy was observed in this patient with Graves’ disease through a serum pepsinogen test, and AIG was suspected due to hypergastrinemia.
Diagnosis of AIG is feasible if anti-parietal cell antibodies or anti-intrinsic factor antibodies are observed in a serological test, using a wide range characteristics of atrophy in the gastric body through an endoscopy, or pernicious anemia, and if there is an accompanying elevated serum gastrin level.16) However, approximately half of patients with AIG are asymptomatic, and even with the occurrence of symptoms, they complain of common digestive symptoms, such as functional dyspepsia or reflux presenting as discomfort after eating.17) Furthermore, AIG at an early stage may appear normal in an endoscopy; hence, there could be a limitation of the diagnosis only using an endoscopy.18) In this patient, no gastrointestinal symptom was observed; thus, if a serum test related to gastritis was not performed during anemia testing, its diagnosis might have been delayed. In a serum test to diagnose AIG at an early stage, a method using a score calculated with hemoglobin, MCV, gastrin, vitamin B12, and chromogranin A was suggested, and the diagnostic usefulness even in a simple scoring method only using hemoglobin, MCV, and gastrin.19) Recently, a method for the early diagnosis was suggested using a questionnaire including neurological symptoms, gastrointestinal symptoms, hematological symptoms, presence of ischemic vascular diseases, presence of AD, infertility or repeated miscarriages, and family history.20)
Currently, no guideline has been established for the diagnosis or treatment of AIG in Korea. If ATD is accompanied by nutrient deficiencies such as anemia of unknown cause occurred, AIG should be suspected and a serum test should be performed. Anemia, severe serological atrophy, and elevated serum gastrin level are significant findings in diagnosing AIG; therefore, efforts are required for a definite diagnosis by identifying anti-parietal cell antibodies and endoscopic biopsies.
Reference
1. Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann 1980;9(4):154–62.
2. Lahner E, Conti L, Cicone F, et al. Thyro-entero-gastric autoimmunity: pathophysiology and implications for patient management. Best Pract Res Clin Endocrinol Metab 2020;34(1):101373.
3. Lenti MV, Rugge M, Lahner E, et al. Autoimmune gastritis. Nat Rev Dis Primers 2020;6(1):56.
4. Rustgi SD, Bijlani P, Shah SC. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Therap Adv Gastroenterol. 2021;14:1–12.
5. Zagari RM, Rabitti S, Greenwood DC, Eusebi LH, Vestito A, Bazzoli F. Systemic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis. Aliment Pharmacol Ther. 2017;46(7):657–67.
6. Lenti MV, Miceli E, Cococcia S, et al. Determinants of diagnostic delay in autoimmune atrophic gastritis. Aliment Pharmacol Ther 2019;50(2):167–75.
7. Rodriguez-Castro KI, Franceschi M, Miraglia C, et al. Autoimmune diseases in autoimmune atrophic gastritis. Acta Biomed 2018;89(8‒S):100–3.
8. Centanni M, Marignani M, Cargano L, et al. Atrophic body gastritis in patients with autoimmune thyroid disease. Arch Intern Med 1999;159(15):1726–30.
9. Pilli T, Dalmazio G, Porcelli B, et al. Screening of organ-specific autoantibodies in a large cohort of patients with autoimmune thyroid disease. Thyroid 2021;31(9):1416–23.
10. Kalkan Ç, Soykan I. Polyautoimmunity in autoimmune gastritis. Eur J Intern Med. 2016;31:79–83.
11. Botello A, Herrán M, Salcedo V, Rodríguez Y, Anaya JM, Rojas M. Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2020;93(4):375–89.
12. Gianoukakis AG, Leigh MJ, Richards P, et al. Characterization of the anemia associated with Graves’ disease. Clin Endocrinol (Oxf) 2009;70(5):781–7.
13. Gianoukakis AG, Gupta S, Tran TN, Richards P, Yehunda M, Tomassetti SE. Graves’ disease patients with iron deficiency anemia: serologic evidence of co-existent autoimmune gastritis. Am J Blood Res 2021;11(3):238–47.
14. Nicolaou A, Thomas D, Alexandraki KI, Sougioultzis S, Tsolakis AV, Kaltsas G. Predictive value of gastrin levels for the diagnosis of gastric Enterochromaffin-like cell hyperplasia in patients with Hashimoto’s thyroiditis. Neuroendocrinology. 2014;99(2):118–22.
15. Venerito M, Radünz M, Reschke K, et al. Autoimmune gastritis in autoimmune thyroid disease. Aliment Pharmacol Ther 2015;41(7):686–93.
16. Terao S, Suzuki S, Yaita H. et al. Multicenter study of autoimmune gastritis in Japan: clinical and endoscopic characteristics. Dig Endosc 2020;32(3):364–72.
17. Carabotti M, Lahner E, Esposito G, Sacchi MC, Severi C, Annibale B. Upper gastrointestinal symptoms in autoimmune gastritis: a cross-sectional study. Medicine (Baltimore) 2017;96(1):e5784.
18. Kotera T, Yamanishi M, Kushima R, Haruma K. Early autoimmune gastritis presenting with a normal endoscopic appearance. Clin J Gastroenterol 2022;15(3):547–52.
19. Miceli E, Padula D, Lenti MV, et al. A laboratory score in the diagnosis of autoimmune atrophic gastritis: a prospective study. J Clin Gastroenterol 2015;49(1):e1–5.
20. Lenti MV, Cococcia S, Miceli E, et al. Red flags for the diagnosis of autoimmune gastritis. Clin Res Hepatol Gastroenterol. 2022;46(1):101780.
Fig. 1. Endoscopic findings. (A) Mild atrophic changed mucosa is observed in the antrum. (B) Extensive atrophic changed mucosa with marked submucosal vasculature is observed in the fundus and body. (C) Focal disappearance of folds with spotty redness are observed in the greater curvature of the gastric body.
Fig. 2. Biopsy results. (A) Mild mucosal destruction with chronic inflammatory cell infiltration of the lamina propria is observed in the antrum. (H&E stain, x100) (B) Mucosal destruction with intense inflammatory cell infiltration of the lamina propria and focal intestinal metaplasia is observed in the body. (H&E stain, x100) (C) Increased neuroendocrine cells with linear neuroendocrine cell hyperplasia are observed in the body. (Chromogranin A stain, x100)
자가면역성위염 환자에서 자가면역성 갑상선 질환 동반 가능성이 높고, 그 반대의 경우도 중요합니다. 자가면역성 갑상선 질환 중 하나인 그레이브씨병 치료 후 생긴 갑상선기능저하로 약물치료 중인 환자에서 시행한 혈청학적 검사에서 자가면역성위염이 의심되어 내시경 검사를 통해 진단 된 환자에 대하여 연구회에서 직접 작성한 case report 입니다. 향후, Case control study가 필요할 것 같습니다.
Patient with Graves’ disease suspected with autoimmune gastritis before endoscopy
Abstract
Autoimmune gastritis (AIG) is a representative disease of atrophic gastritis caused by destruction of parietal cell in the fundus and body of stomach as a result of a chronic inflammatory responses through an immune reaction. Since it is characterized by extensive atrophy of the body, endoscopic findings are an important clue in diagnosis. Diagnosis is made through serological and histological tests based on endoscopic findings, but it can be accompanied by autoimmune diseases such as autoimmune thyroid diseases (ATD), and vice-versa can be suspected. In addition, AIG often does not have clear clinical symptoms, and diagnosis is likely to be delayed because it is difficult to suspect before symptoms due to accompanying diseases. We report in a patient with Graves’ disease, one of the ATD, severe serological atrophy, hypergastrinemia, and anti-parietal cell antibody positive was suspected through serological tests, and then diagnosed through endoscopy and biopsy.
Key words: Autoimmune disease; Gastritis; Graves’ disease; Gastrin
Introduction
The intestine, stomach, and thyroid gland develop from the same origin at the embryonic stage; thus, autoimmune thyroid diseases (ATD) such as Hashimoto’s thyroiditis and Graves’ disease, which can be accompanied by autoimmune gastritis (AIG) or celiac disease, were previously known as “thyro-gastric syndrome.”1,2) AIG is an immune-mediated disease with consistant inflammatory responses occurring through auto-activated T cells caused by reacting with antibodies that recognize the H+/K+ ATPase in parietal cells secreting gastric acid which leads gastric corpus atrophy.3) The gradual parietal cell destruction subsequently leads to a remarkable decline in gastric acid and intrinsic factor secretions, thereby resulting in iron, vitamin B12, and micronutrient deficiencies, with a possibility of anemia, sensory and peripheral neuropathy, infertility, and repeated miscarriages.4) Owing to extensive histopathologic evolution of gastric corpus atrophy, injured chief cells and increased gastrin cell expressions exhibit a notable decline in serum pepsinogen I and pepsinogen I/II ratio and an elevated gastrin in the blood through a serum test, which are characteristics of serological atrophic gastritis.3-5) However, AIG does not present with distinct clinical signs and typically occurs asymptomatically, and then the final diagnosis is delayed owing to misdiagnose it as functional dyspepsia, gastroesophageal reflux disease, or anemia.6) The standard diagnosis method of AIG is to perform an endoscopy and biopsy to determine inflammatory conditions in the gastric corpus, whereas a serum test and a positive anti-parietal cell antibody test preferentially could be performed if an autoimmune disease (AD) is suspected highly accompanied by AIG.7) This is a case report of a patient with Graves’ disease, confirmed to have a positive anti-parietal cell antibody and severe serological atrophy based on a serum test to identify the occurrence of AIG, and then an endoscopy was performed to make a histological diagnosis.
Case report
A 44-year-old woman diagnosed with Graves’ disease approximately 8 years before the study period was treated with radioactive iodine. Therefore, she developed hypothyroidism and was consequently consuming 0.1 mg of synthyroid. The patient underwent a blood transfusion owing to severe iron-deficiency anemia during pregnancy and was intermittently taking iron supplements. She had no gastrointestinal symptoms and has not taken gastric acid secretion inhibitors or receiving treatment for Helicobacter pylori (H. pylori).
A blood test was performed to assess anemia and thyroid levels, showing the following results: hemoglobin, 7.5 (reference range, 12.0–16.0) g/dL; hematocrit, 25.1% (37.0–40.0%); mean corpuscular volume (MCV), 73.2 (80.0–100.0) Fl; mean corpuscular hemoglobin (MCH), 21.6 (27.0–34.0) pg; MCH concentration, 29.5 (32.0–36.0) g/dL; Fe, 13 (33–193) μg/dL; ferritin, 8.10 (13.0–150.0) ng/mL; transferrin and iron-binding capacity, 371 (228–428) μg/dL; and vitamin B12, 403 (180–914) pg/mL; thus, it was diagnosed as iron-deficiency anemia. Furthermore, the results presented free T4 of 1.32 (reference range, 0.85–1.50) ng/dL; T3, 1.62 (0.58–1.62) ng/mL; thyroid stimulating hormone (TSH), <0.05 (0.25–5.00); TSH receptor antibody, 2.26 (0.0–1.22) IU/L; anti-thyroid-peroxidase antibody, 10.1 (0.0–34.0) IU/mL; and thyroglobulin antibody, 13.9 (0.0–115.0) IU/mL, indicating that the thyroid gland function was well maintained after a radioactive iodine treatment. Although no distinct gastrointestinal symptom was observed, thus a serum test was performed to determine the occurrence of accompanying AIG. The results demonstrated pepsinogen I, II, and I/II ratio was 28.7 ng/mL, 26.3 ng/mL, and 1.1, respectively, presenting very low pepsinogen I level and pepsinogen I/II ratio and elevated serum gastrin level to 792 (13–115) pg/mL. Anti-H. pylori antibodies were measured using H. pylori IgG Immulite® 2000 (Siemens, USA), presenting a positive result of 4.27 U/mL (negative, <0.90 U/mL; equivocal, 0.90–1.09 U/mL; positive, ≥1.10 U/mL). Additionally, an anti-parietal cell antibody test using immunofluorescence assay (KALLESTAD Mouse Stomach/Kidney, Bio RAD, USA) revealed positive results; thus, autoimmune hyperthyroidism accompanied by AIG was suspected.
Endoscopy to diagnose AIG and identify the presence of accompanying H. pylori infection revealed mild atrophy in the gastric antrum (Fig. 1A). However, submucosal blood vessels were markedly observed in the gastric fundus and body, showing corpus-dominant atrophy with gastric-fold disappearance (Fig. 1B). Spotty redness caused by H. pylori was observed in the greater curvature of the gastric body (Fig. 1C). Therefore, the rapid urease test was performed, which was confirmed to be positive. Biopsies were obtained from the gastric antrum and body, respectively. Results showed some atrophic changes and inflammatory cell infiltration in the mucosa of the gastric antrum (Fig. 2A), whereas atrophy was considerably severe in the mucosa at the greater and lesser curvatures of the gastric body, and inflammatory cell infiltration was distinct in the lamina propria (Fig. 2B). The immunohistochemistry results using chromogranin revealed proliferation of enterochromaffin-like cells in the gastric body (Fig. 2C). The patient was eventually diagnosed with AIG and started to take iron supplements and is receiving outpatient follow-up care after being prescribed medications for H. pylori eradication.
Discussion
ATD are accompanied with AIG in 35% of patients, and anti-parietal cell antibodies are most commonly accompanied with organ-specific autoantibodies.8,9) More than half of the patients with AIG may develop AD, and ATD are the most common comorbidity in approximately >36% of patients.10) Graves’ disease is the most common type of ATD and is accompanied by anemia in >30%.11,12) Regarding the anemia pattern, the chronic disease-like “Graves’ anemia” is the most common, which maintains normal thyroid levels post-treatment and improves in most cases.12) In this patient, no medical record was reviewed before radioactive iodine treatment for Graves’ disease; thus, whether there was Graves’ anemia or not remains unclear. However, considering that normal thyroid levels were maintained post-treatment and a markedly reduced MCV and ferritin level was observed, anemia at the time of hospital visit was diagnosed as iron-deficiency anemia rather than Graves’ anemia. When Graves’ disease is accompanied by iron-deficiency anemia, the expression of anti-parietal antibodies is increased in many cases, which are characteristics of AIG, as well as elevated serum gastrin.13) The proliferation of enterochromaffin-like cells can be observed, which may progress to neuroendocrine tumors in patients with ATD associated with AIG, and in such histological changes, the elevated serum gastrin is diagnostically significant.10,12-14) Furthermore, in patients with ATD, a serum pepsinogen test can be used as an important biomarker that confirms severe histological atrophy, irrespective of H. pylori infection.15) Severe atrophy was observed in this patient with Graves’ disease through a serum pepsinogen test, and AIG was suspected due to hypergastrinemia.
Diagnosis of AIG is feasible if anti-parietal cell antibodies or anti-intrinsic factor antibodies are observed in a serological test, using a wide range characteristics of atrophy in the gastric body through an endoscopy, or pernicious anemia, and if there is an accompanying elevated serum gastrin level.16) However, approximately half of patients with AIG are asymptomatic, and even with the occurrence of symptoms, they complain of common digestive symptoms, such as functional dyspepsia or reflux presenting as discomfort after eating.17) Furthermore, AIG at an early stage may appear normal in an endoscopy; hence, there could be a limitation of the diagnosis only using an endoscopy.18) In this patient, no gastrointestinal symptom was observed; thus, if a serum test related to gastritis was not performed during anemia testing, its diagnosis might have been delayed. In a serum test to diagnose AIG at an early stage, a method using a score calculated with hemoglobin, MCV, gastrin, vitamin B12, and chromogranin A was suggested, and the diagnostic usefulness even in a simple scoring method only using hemoglobin, MCV, and gastrin.19) Recently, a method for the early diagnosis was suggested using a questionnaire including neurological symptoms, gastrointestinal symptoms, hematological symptoms, presence of ischemic vascular diseases, presence of AD, infertility or repeated miscarriages, and family history.20)
Currently, no guideline has been established for the diagnosis or treatment of AIG in Korea. If ATD is accompanied by nutrient deficiencies such as anemia of unknown cause occurred, AIG should be suspected and a serum test should be performed. Anemia, severe serological atrophy, and elevated serum gastrin level are significant findings in diagnosing AIG; therefore, efforts are required for a definite diagnosis by identifying anti-parietal cell antibodies and endoscopic biopsies.
Reference
1. Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann 1980;9(4):154–62.
2. Lahner E, Conti L, Cicone F, et al. Thyro-entero-gastric autoimmunity: pathophysiology and implications for patient management. Best Pract Res Clin Endocrinol Metab 2020;34(1):101373.
3. Lenti MV, Rugge M, Lahner E, et al. Autoimmune gastritis. Nat Rev Dis Primers 2020;6(1):56.
4. Rustgi SD, Bijlani P, Shah SC. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Therap Adv Gastroenterol. 2021;14:1–12.
5. Zagari RM, Rabitti S, Greenwood DC, Eusebi LH, Vestito A, Bazzoli F. Systemic review with meta-analysis: diagnostic performance of the combination of pepsinogen, gastrin-17 and anti-Helicobacter pylori antibodies serum assays for the diagnosis of atrophic gastritis. Aliment Pharmacol Ther. 2017;46(7):657–67.
6. Lenti MV, Miceli E, Cococcia S, et al. Determinants of diagnostic delay in autoimmune atrophic gastritis. Aliment Pharmacol Ther 2019;50(2):167–75.
7. Rodriguez-Castro KI, Franceschi M, Miraglia C, et al. Autoimmune diseases in autoimmune atrophic gastritis. Acta Biomed 2018;89(8‒S):100–3.
8. Centanni M, Marignani M, Cargano L, et al. Atrophic body gastritis in patients with autoimmune thyroid disease. Arch Intern Med 1999;159(15):1726–30.
9. Pilli T, Dalmazio G, Porcelli B, et al. Screening of organ-specific autoantibodies in a large cohort of patients with autoimmune thyroid disease. Thyroid 2021;31(9):1416–23.
10. Kalkan Ç, Soykan I. Polyautoimmunity in autoimmune gastritis. Eur J Intern Med. 2016;31:79–83.
11. Botello A, Herrán M, Salcedo V, Rodríguez Y, Anaya JM, Rojas M. Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2020;93(4):375–89.
12. Gianoukakis AG, Leigh MJ, Richards P, et al. Characterization of the anemia associated with Graves’ disease. Clin Endocrinol (Oxf) 2009;70(5):781–7.
13. Gianoukakis AG, Gupta S, Tran TN, Richards P, Yehunda M, Tomassetti SE. Graves’ disease patients with iron deficiency anemia: serologic evidence of co-existent autoimmune gastritis. Am J Blood Res 2021;11(3):238–47.
14. Nicolaou A, Thomas D, Alexandraki KI, Sougioultzis S, Tsolakis AV, Kaltsas G. Predictive value of gastrin levels for the diagnosis of gastric Enterochromaffin-like cell hyperplasia in patients with Hashimoto’s thyroiditis. Neuroendocrinology. 2014;99(2):118–22.
15. Venerito M, Radünz M, Reschke K, et al. Autoimmune gastritis in autoimmune thyroid disease. Aliment Pharmacol Ther 2015;41(7):686–93.
16. Terao S, Suzuki S, Yaita H. et al. Multicenter study of autoimmune gastritis in Japan: clinical and endoscopic characteristics. Dig Endosc 2020;32(3):364–72.
17. Carabotti M, Lahner E, Esposito G, Sacchi MC, Severi C, Annibale B. Upper gastrointestinal symptoms in autoimmune gastritis: a cross-sectional study. Medicine (Baltimore) 2017;96(1):e5784.
18. Kotera T, Yamanishi M, Kushima R, Haruma K. Early autoimmune gastritis presenting with a normal endoscopic appearance. Clin J Gastroenterol 2022;15(3):547–52.
19. Miceli E, Padula D, Lenti MV, et al. A laboratory score in the diagnosis of autoimmune atrophic gastritis: a prospective study. J Clin Gastroenterol 2015;49(1):e1–5.
20. Lenti MV, Cococcia S, Miceli E, et al. Red flags for the diagnosis of autoimmune gastritis. Clin Res Hepatol Gastroenterol. 2022;46(1):101780.
Fig. 1. Endoscopic findings. (A) Mild atrophic changed mucosa is observed in the antrum. (B) Extensive atrophic changed mucosa with marked submucosal vasculature is observed in the fundus and body. (C) Focal disappearance of folds with spotty redness are observed in the greater curvature of the gastric body.
Fig. 2. Biopsy results. (A) Mild mucosal destruction with chronic inflammatory cell infiltration of the lamina propria is observed in the antrum. (H&E stain, x100) (B) Mucosal destruction with intense inflammatory cell infiltration of the lamina propria and focal intestinal metaplasia is observed in the body. (H&E stain, x100) (C) Increased neuroendocrine cells with linear neuroendocrine cell hyperplasia are observed in the body. (Chromogranin A stain, x100)
