Explore the vast range of titles available.

Pernicious anemia is a macrocytic anemia caused by vitamin B12 deficiency that results from a lack of intrinsic factor. Lack of intrinsic factor may be caused by atrophic gastritis and damage to the oxyntic mucosa and parietal cells, which normally produce hydrochloric acid and intrinsic factor. Glossitis presents in up to 25% of people with pernicious anemia, initially as bright red plaques that may evolve into atrophy of the lingual papillae. Oral manifestations of pernicious anemia, including glossitis and stomatitis, may occur in the absence of anemia and represent an early clinical sign of vitamin B12 deficiency. Other causes of glossitis include nutritional deficiencies of vitamin B12, folic acid, riboflavin and niacin. Here, Kobayashi and Iwasaki examine the case of a 69-year-old Japanese woman with pernicious anemia.

Background Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. Methods Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. Results Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (OR SD , 1.12; 95% CI 1.04, 1.21, p  = 0.003) and colorectal cancer (OR SD 1.16; 95% CI 1.06, 1.26, p  = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined OR SD was 1.16 (95% CI 1.08, 1.25, p  < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. Conclusions These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

Background Pernicious anemia, also called Biemer’s disease, is an autoimmune disease and the most common cause of cobalamin deficiency globally. Various genetic, environmental, and immunological factors interplay to lead to its presentation. Pernicious anemia has a myriad of presentations, which can range from hematological and skin-related to neurological. Pernicious anemia has been reported among people of all ages worldwide, especially those over 60 years old. Its prevalence in the general population is about 0.1% and 1.9% for elderly patients over 60 years old. Like most other autoimmune diseases, females are more affected than males. However, there are case reports of pernicious anemia occurring in individuals at 40 years of age. The prevalence of pernicious anemia in Africa has been reportedly low, possibly owing to underdiagnosis. Case presentation This case identifies a 51-year-old Ugandan man from the tribe of Ankole who presented with lower limb weakness for about 2 months. He had a similar presentation 7 years prior for which he was treated for vitamin B12 deficiency. Initial blood counts revealed macrocytic anemia. Considering the recurrence of symptoms, serum cobalamin levels and serum intrinsic factor autoantibodies were tested and the diagnosis of pernicious anemia was confirmed. The patient improved on parenteral methylcobalamin therapy. Conclusion This case report highlights the importance of a high index of suspicion in early diagnosis of vitamin B12 deficiency as a cause of neurological symptoms and in considering the diagnosis and empiric therapy for pernicious anemia in a resource-limited context.

To the Editor: Within a 3-week period, two women, 46 and 48 years of age, presented with peripheral neuropathy and associated pancytopenia with macrocytic anemia. Clinical suspicion for pernicious anemia was high, but vitamin B 12 levels were 1644 pg per milliliter (1228 pmol per liter) and 1321 pg per milliliter (975 pmol per liter), respectively (reference range, 246 to 1320 pg per milliliter [181 to 974 pmol per liter]). On subsequent bone-marrow evaluation, specimens from both patients showed profound megaloblastic features. Additional findings on laboratory tests included elevated levels of homocysteine and methylmalonic acid combined with detection of intrinsic . . .

Background Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case–control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is due to genetic and acquired factors (poor diet in folate and vitamin B12, older age, renal impairment, thyroid diseases, and malignancies) induced by the intake and the concentrations of vitamin B9 or B12 in the majority of cases. Cases presentation We report the cases of four Moroccan patients who presented with acute vein thrombosis of different sites: a 34-year-old man, a 60-year-old man, a 58-year-old man, and a 47-year-old woman. All patients had a low level of cobalamin with marked hyperhomocysteinemia with normal serum and red cell folic acid. Venous thrombosis revealed pernicious anemia in all patients. Their low levels of cobalamin, atrophic gastritis, and positive results for gastric parietal cell antibodies confirmed the diagnosis of pernicious anemia. There was no evidence of immobilization, recent surgery, malignancy, antiphospholipid antibody, myeloproliferative disorder, or hormone replacement therapy. No deficiencies in protein C and protein S were detected; they had normal antithrombin III function and factor V Leiden; no prothrombin gene mutations were detected. Treatment included orally administered anticoagulation therapy and cobalamin supplementation. The outcome was favorable in all cases. Conclusions These reports demonstrate that pernicious anemia, on its own, can lead to hyperhomocysteinemia that is significant enough to lead to thrombosis. Understanding the molecular pathogenesis of the development of thrombosis in patients with hyperhomocysteinemia related to Biermer disease would help us to identify patients at risk and to treat them accordingly. The literature concerning the relationship between homocysteine and venous thrombosis is briefly reviewed.

INTRODUCTION: The aim of the study was to determine the frequency of occurrence of antibodies participating in the development of endocrine diseases in patients with autoimmune haematopoietic disease, thus documenting the potential suitability of specific diagnostic and screening tests. MATERIAL AND METHODS: The study group consisted of 124 persons (men and women) with newly diagnosed pernicious anaemia (PA) and a control group (C) of 41 healthy people. Antibodies against: intrinsic factor (IFAb), gastric parietal cells (APCA), thyroid peroxidase (TPOAb), thyroglobulin (TgAb), adrenal cortex (AdrenalAb), and pituitary anterior lobe (PituitaryAb) were determined in the blood. RESULTS: 1. The risk of the presence of antibodies against endocrine glands in patients with PA can be classified in order: TPOAb and/or TgAb — 41.1%, TPOAb — 36.3%, TgAb — 25.0%, TPOAb and TgAb — 20.2%, AdrenalAb — 1.6%, PituitaryAb — 0.8%. 2. TPOAb and/or TgAb (mainly TPOAb) are more frequently present in patients with PA, who have IFAb and/or APCA. This correlation is most evident in patients with simultaneous occurrence of IFAb and APCA. 3. Among patients with PA, the simultaneous presence of antibodies IFAb and/or APCA with TPOAb and/or TgAb antibodies is most likely in women over 45 years of age. 4. In group C, 12% had at least one of two antithyroid antibodies (TgAb twice as often as TPOAb), and 2.4% had both. AdrenalAb and PituitaryAb are not found in healthy persons. CONCLUSIONS: In patients with PA, a screening for autoimmune thyroid disease is justified, which should first involve the determination of TPOAb (further TgAb) in the blood. The assessment of antithyroid antibodies should be recommended primarily to patients with PA, who have IFAb and/or APCA, and in particular those with concurrent IFAb and APCA.

Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15·8 (sd 14·7) nmol/l in 1995 to 31·1 (sd 26·2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1·50 (95 % CI 0·91, 2·46) v. 1·45 (95 % CI 1·19, 1·76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2·46; 95 % CI 0·90, 6·71) v. (1·56; 95 % CI 1·30, 1·88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

Pernicious anaemia is an autoimmune disease caused by intrinsic factor antibody; it leads to vitamin B12 deficiency and is marked by ineffective erythropoiesis. Haematological features reveal macrocytosis, hyperchromasia and hypersegmented neutrophils. Schistocytes are typically seen in microangiopathy, such as in thrombotic thrombocytopaenic purpura (TTP)/haemolytic uraemic syndrome or disseminated intravascular haemolysis (DIC). We report a case of a patient with severe anaemia who presented to the emergency room. Peripheral smear revealed macrocytosis, hypersegmented neutrophils and marked schistocytosis. The patient also had high reticulocyte count with high serum lactate dehydrogenase, elevated D-dimer, low fibrinogen and low haptoglobin. Vitamin B12 level came back low and the presence of intrinsic factor antibody confirmed pernicious anaemia. ADAMTS13 level was noted to be mildly reduced, which raised the suspicion of the association of acquired TTP with pernicious anaemia. Acquired TTP is another autoimmune disorder and its association with pernicious anaemia needs further evaluation.

Background:The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific.Methods:The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels.Results:Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA.Conclusions:This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.