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 B₁₂ 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 B₁₂ deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.

Gender differences and microbiota are gaining increasing attention. This study aimed to assess gender differences in gastric bacterial microbiota between subjects with healthy stomachs and those with autoimmune atrophic gastritis. This was a post hoc analysis of 52 subjects undergoing gastroscopy for dyspepsia (57.7% healthy stomach, 42.3% autoimmune atrophic gastritis). Gastric biopsies were obtained for histopathology and genomic DNA extraction. Gastric microbiota were assessed by sequencing the hypervariable regions of the 16SrRNA gene. The bacterial profile at the phylum level was reported as being in relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for the female and male gender. Results showed that women with healthy stomachs had a higher gastric bacterial abundance and less microbial diversity compared to men. Likely due to hypochlorhydria and the non-acid intragastric environment, autoimmune atrophic gastritis seems to reset gender differences in gastric bacterial abundance and reduce biodiversity in males, showing a greater extent of dysbiosis in terms of reduced biodiversity in men. Differences between gender on taxa frequency at the phylum and genus level in healthy subjects and autoimmune atrophic gastritis were observed. The impact of these findings on the gender-specific natural history of autoimmune atrophic gastritis remains to be elucidated; in any case, gender differences should deserve attention in gastric microbiota studies.

Corpus Atrophic Gastritis (CAG) is characterised by iron malabsorption leading to iron deficiency anaemia (IDA), which rarely responds to oral therapy. Ferric carboxymaltose (FCM), shown to be a safe and effective intravenous iron therapy in other diseases, has not been investigated yet in CAG. Thus, we aimed to assess the safety and efficacy of FCM in CAG-related IDA. A retrospective study on 91 patients identified CAG as the only cause of IDA treated with FCM. Twenty-three were excluded for incomplete follow-up. Sixty-eight were evaluated for safety and efficacy, while three were evaluated for safety only due to infusion interruption for side effects. Haemoglobin and iron storage were evaluated pre-infusion (T0), at 4 weeks (T4) and 12 weeks (T12) after infusion. An eventual IDA relapse was analysed. Two cases reported mild side effects. Haemoglobin significantly increased at T4, and T12, reaching +3.1 g/dL. Ferritin increased at T4, decreasing at T12, while transferrin saturation increased progressively until reaching a plateau. IDA relapsed in 55.4% of patients at a mean of 24.6 months. The only factor associated with relapse was female gender [OR (95% CI): 6.6 (1.5–28.6)]. FCM proved to be safe and effective in treating CAG-related IDA, ensuring quick and long-lasting recovery.

Iron-deficiency anemia in the elderly may be due to numerous gastrointestinal conditions. Anemia is frequent in celiac disease (CD); however, the use of routine duodenal biopsies, independently of age or serology, is debated. To determine the diagnostic yield of routine duodenal biopsies in adult and elderly patients with no bleeding anemia, a cross-sectional study analyzing 7968 gastroscopies (2017–2020) was performed; 744 were for anemia and 275 were excluded (GI bleeding or without duodenal biopsies). Of the 469 included patients, clinical, endoscopic, and histological features were analyzed in groups with or without histopathological changes in the duodenal mucosa (DM). Univariate/multivariate analyses were performed. Of the 469 patients, 41 (8.7%) had DM histopathological changes, 12 (2.6%) had CD, 26 (5.5%) had duodenal intraepithelial lymphocytosis (DIL), and 3 had (0.6%) other conditions. They were younger compared to patients with normal DM. DM histopathology was significantly inversely correlated with age group, with prevalences of 27%, 20%, 12.5%, 10%, and 2.5%, in the 80-year age groups, respectively (p = 0.0010). Logistic-regression models showed that anemic patients aged >60, >70, or >80 years with endoscopically normal DM had a progressively three- to four-fold higher probability of having normal duodenal histology. In adults, anemic patients without bleeding, age and endoscopically normal DM are predictors of normal DM histology. In >70-year anemic patients, negligible DM pathology was found. The results suggest that routine duodenal biopsies are questionable in elderly anemic patients

We would like to thank Greenaway et al.

Background and Objectives: Corpus atrophic gastritis (CAG) is associated with vitamin B₁₂ deficiency due to impaired gastric acid and intrinsic factor secretion. Untreated vitamin B₁₂ deficiency can lead to pernicious anemia, severe neurological consequences, and acute cardiocerebral-vascular events. Timely vitamin B₁₂ supplementation is relevant; however, the dosage of intramuscular (IM) vitamin B₁₂ supplementation has not been standardized to date. The objective was to assess the efficacy of a 1st and 2nd treatment schedule of IM-cyanocobalamin treatment in CAG patients with vitamin B₁₂ deficiency at long-term follow-up and to identify the predictors of increased cyanocobalamin requirement. Methods: This monocentric real-life cohort study included 213 CAG patients with vitamin B₁₂ deficiency. Inclusion criteria were adult age, histological diagnosis of CAG with vitamin B₁₂ deficiency (<220 pg/mL), and follow-up of more than 12 months. The 1st-treatment-schedule (TxA) was 5000 µg IM cyanocobalamin every 5 days for 3 times, followed by 5000 µg IM cyanocobalamin every 3 mos (20,000 µg/yr); the 2nd-treatment-schedule (TxB) was 5000 µg IM cyanocobalamin every 5 days for 3 times, followed by 5000 µg IM cyanocobalamin every 2 mos (30,000 µg/yr). The treatment endpoint was serum vitamin B₁₂ normalization. Clinical-biochemical follow-up was scheduled every 12 ± 6 mos: patients who satisfied the endpoint maintained the TxA, otherwise, TxB was prescribed. Results: Of the 213 CAG patients with vitamin B₁₂ deficiency, 48.3% had anemia, and 26.3% macrocytosis without anemia. TxA efficaciously corrected vitamin B₁₂ deficiency in 146 (68.5%) patients, maintaining efficacy until the longest available follow-up (42.2 ± 2.6 months). The remaining 67 patients (31.5%) were switched to TxB due to persistent vitamin B₁₂ deficiency observed at 12 (6–36) months and were maintained until the longest available follow-up (50.2 ± 4.1 months). At the longest available follow-up, a significant increase in Hb (TxA: 11.9 ± 0.2 to 13.1 ± 0.1 g/dL, p < 0.001; TxB: 12.2 ± 0.3 to 13.6 ± 0.2 g/dL, p = 0.003) and serum vitamin B₁₂ (TxA: 168 ± 7 to 402 ± 19 pg/mL, p < 0.0001; TxB: 157 ± 12 to 340 ± 24 pg/mL, p < 0.0001) was shown in both schedules. A significant decrease in MCV was shown in TxB only (p = 0.0003). In logistic regression, switching to TxB was significantly associated with severe corpus intestinal metaplasia (OR 11.0, 95% CI 2.8–43.7), macrocytosis at CAG diagnosis (OR 2.7, 95% CI 1.2–6.3), and male sex (OR 2.4, 95% CI 1.1–5.2). Conclusions: In this real-world setting, at long-term follow-up, nearly 70% of CAG patients with vitamin B₁₂ deficiency restored their vitamin B₁₂ levels with 20,000 µg/yr of cyanocobalamin, while the remaining 30% required 30,000 µg/yr. Male vitamin B₁₂-deficient CAG patients with advanced gastric damage and severe macrocytosis required higher dosages of cyanocobalamin. They should be carefully monitored to avoid suboptimal supplementation and potentially dangerous consequences of vitamin B₁₂ deficiency.