Cell Blood Count Alterations and Patterns of Anaemia in Autoimmune Atrophic Gastritis at Diagnosis: A Multicentre Study

Background: Autoimmune atrophic gastritis (AAG) leads to iron and/or vitamin B12 malabsorption, with subsequent haematological alterations which could represent the sole clinical manifestation. We aimed to assess patterns of anaemia and micronutrient deficiencies in patients with AAG at the time of diagnosis. Methods: Observational, multicentre, cross-sectional study including consecutive adult patients diagnosed with AAG within the last ten years. Cell blood count, red cell distribution width, serum vitamin B12, and ferritin were collected. Multivariate analysis for predictive factors of anaemia was computed. Results: 654 AAG patients (mean age 59.2 \ub1 13.8 years, female (F): male (M) ratio = 2.3:1) were included. Anaemia was present in 316 patients (48.3%; mean age 60.1 \ub1 15.8 years, F:M ratio = 2.3:1). Pernicious anaemia (132/316 cases, 41.7%) was more common in males (27.1% versus 12.4%; p = 0.001) and in older patients (63.0 \ub1 14.6 versus 58.9 \ub1 14.9 years; p = 0.014), while iron deficiency anaemia (112/316 cases, 35.4%) was more common in females (16.9% versus 10.0%; p = 0.039) and in younger patients (56.8 \ub1 16.6 versus 60.2 \ub1 14.6 years; p = 0.043). The prevalence of iron deficiency was equally distributed between anaemic and non-anaemic patients (p = 0.9). Anisocytosis (odds ratio: 10.65, 95% confidence interval: 6.13-18.50, p < 0.0001) was independently associated with anaemia. Conclusions: Anaemia is a common manifestation in AAG patients, mostly due to micronutrient deficiencies. Scant haematologic alterations and micronutrient deficiencies may precede overt anaemia

Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy

Background: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. Aims: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. Methods: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. Results: A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. Conclusion: We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding

Clinical phenotype and mortality in patients with idiopathic small bowel villous atrophy: a dual-centre international study

Objective Causes of small-bowel villous atrophy (VA) include coeliac disease (CD), its complications and other rare non-coeliac enteropathies. However, forms of VA of unknown aetiology may also exist. We defined them as idiopathic VA (IVA). To retrospectively classify the largest cohort of IVA patients and compare their natural history with CD. Methods Notes of 76 IVA patients attending two tertiary centres between January 2000 and March 2019 were retrospectively reviewed. CD, its complications and all the known causes of VA were excluded in all of them. Persistence of VA during follow-up and lymphoproliferative features were used to retrospectively classify IVA, as follows. Group 1: IVA with spontaneous histological recovery (50 patients). Group 2: persistent IVA without lymphoproliferative features (14 patients). Group 3: persistent IVA with lymphoproliferative features (12 patients). Survival was compared between IVA groups and 1114 coeliac patients. HLA was compared between IVA patients, coeliac patients and appropriate controls. Results Five-year survival was 96% in IVA group 1, 100% in IVA group 2, 27% in IVA group 3 and 97% in CD. On a multivariate analysis hypoalbuminemia (P = 0.002) and age at diagnosis (P = 0.04) predicted mortality in IVA. Group 2 showed association with HLA DQB1*0301 and DQB1*06. Conclusion IVA consists of three groups of enteropathies with distinct clinical phenotypes and prognoses. Mortality in IVA is higher than in CD and mainly due to lymphoproliferative conditions necessitating more aggressive therapies

How I treat enteropathy-associated T-cell lymphoma

Enteropathy-associated T-cell lymphoma (EATL) is a complication of celiac disease (CD). This tumor derives from the neoplastic transformation of aberrant intraepithelial T lymphocytes emerging in celiac patients unresponsive to a gluten-free diet. Poor adherence to a gluten-free diet, HLA-DQ2 homozygosity, and late diagnosis of CD are recognized as risk factors for malignant evolution of CD. Recurrence of diarrhea, unexplained weight loss, abdominal pain, fever, and night sweating should alert physicians to this complication. The suspicion of EATL should lead to an extensive diagnostic workup in which magnetic resonance enteroclysis, positron emission tomography scan, and histologic identification of lesions represent the best options. Treatment includes high-dose chemotherapy preceded by surgical resection and followed by autologous stem cell transplantation, although biologic therapies seem to be promising. Strict adherence to a gluten-free diet remains the only way to prevent EATL

A reassessment of splenic hypofunction in celiac disease

Objectives: Because there is controversy regarding the prevalence, familial occurrence, and possible factors inducing splenic hypofunction in celiac disease, we have reassessed them in a large series of untreated patients and their first-degree relatives. Methods: Pitted red cell counting was used to measure splenic function and the effect that age at diagnosis has on it, while severity of intestinal lesions and nutritional status were estimated by multiple linear regression analysis. Moreover, serum tuftsin activity was assayed by measuring its ability to stimulate phagocytosis of opsonized Staphylococcus aureus. Results: We found that 32.8% of untreated celiacs and none of their relatives had pitted red cell values in the range of splenic hypofunction (>4%). Only age at diagnosis, but not the other two covariates, was significantly associated with the degree of splenic hypofunction. Tuftsin activity was depressed in celiac disease and this reduction was significantly greater in hyposplenic patients. Conclusions: In celiac disease the prevalence of splenic hypofunction is lower than formerly believed. The duration of preexposure to gluten is a crucial factor for the prevalence and severity of this complication that does not affect celiac relatives. In celiac disease splenic hypofunction is accompanied by a reduced phagocyte activity linked to the decreased release of tuftsin