Thyroid function, pernicious anemia and erythropoiesis: a two-sample Mendelian randomization study.

Autoimmune thyroid disease (AITD) and pernicious anemia (PA) often coexist, but the directionality is unknown. In a two-sample Mendelian randomization (MR) analysis, using summary statistics from large genome-wide association studies (GWASs) in Europeans (N = 49 269-755 406), we examined the genetic associations between thyroid function, PA and markers of erythropoiesis. We performed inverse variance weighted random-effects MR, several sensitivity MR analyses, and bidirectional MR and MR Steiger for directionality. AITD and PA were associated bidirectionally (P ≤ 8 × 10-6). Neither euthyroid thyroid stimulating hormone (TSH) nor free thyroxine (FT4) were causally associated with PA. One standard deviation (SD) increase in euthyroid FT4 regulated by genetic variants in deiodinases 1 and 2 genes (DIO1/DIO2), corresponding to low-normal free triiodothyronine (FT3) levels, was causally associated with a pernicious/macrocytic anemia pattern, i.e. decreased erythrocyte counts (rank-based inverse normal transformed ß = -0,064 [95% confidence interval: -0,085, -0,044], P = 8 × 10-10) and hemoglobin (-0.028 [-0.051, -0.005], P = 0.02) and increased mean corpuscular hemoglobin (0.058 [0.025, 0.091], P = 5 × 10-4) and mean corpuscular volume levels (0.075 [0.052, 0.098], P = 1 × 10-8). Meanwhile, subclinical hyperthyroidism mirrored that pattern. AITD was causally associated with increased erythrocyte distribution width (P = 0.007) and decreased reticulocyte counts (P ≤ 0.02), whereas high-normal FT4 regulated by DIO1/DIO2 variants was causally associated with decreased bilirubin (-0.039 (-0.064, -0.013), P = 0.003). In conclusion, the bidirectional association between AITD and PA suggests a shared heritability for these two autoimmune diseases. AITD was causally associated with impaired erythropoiesis and not autoimmune hemolysis. Additionally, in euthyroid individuals, local regulation of thyroid hormones by deiodinases likely plays a role in erythropoiesis.

Autoimmune conditions and gastric cancer risk in a population-based study in the United Kingdom.

BACKGROUND: Although overall incidence of gastric cancer is decreasing, incidence has been increasing among young people in some Western countries. This trend may stem from the increase in autoimmune conditions. METHODS: A nested case-control study of gastric cancer in UK Clinical Practice Research Datalink. Up to ten cancer-free controls were matched to cases by age and sex. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between analyzable autoimmune conditions (n = 34) and gastric cancer with Bonferroni correction. We evaluated associations between pernicious anaemia and other conditions. A meta-analysis of published prospective studies and ours was conducted. RESULTS: Among 6586 cases (1156 cardia, 1104 non-cardia, and 4334 overlapping/unspecified tumours) and 65,687 controls, any autoimmune condition was associated with gastric cancer (OR = 1.10; 95% CI: 1.01-1.20). Individuals with pernicious anaemia had higher gastric cancer risk than those without (OR = 2.75; 2.19-3.44). Among controls, pernicious anaemia was associated with seven other conditions (OR range: 2.21-29.80). The pooled estimate for any autoimmune condition and gastric cancer was 1.17 (1.14-1.21; n = 47,126 cases). CONCLUSION: Autoimmunity increases gastric cancer risk. Some autoimmune conditions may be indirectly associated with gastric cancer via pernicious anaemia. Pernicious anaemia could be considered for gastric cancer risk stratification and screening.

Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK.

BACKGROUND: A rise in the incidence of some autoimmune disorders has been described. However, contemporary estimates of the overall incidence of autoimmune diseases and trends over time are scarce and inconsistent. We aimed to investigate the incidence and prevalence of 19 of the most common autoimmune diseases in the UK, assess trends over time, and by sex, age, socioeconomic status, season, and region, and we examine rates of co-occurrence among autoimmune diseases. METHODS: In this UK population-based study, we used linked primary and secondary electronic health records from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex and ethnicity. Eligible participants were men and women (no age restriction) with acceptable records, approved for Hospital Episodes Statistics and Office of National Statistics linkage, and registered with their general practice for at least 12 months during the study period. We calculated age and sex standardised incidence and prevalence of 19 autoimmune disorders from 2000 to 2019 and used negative binomial regression models to investigate temporal trends and variation by age, sex, socioeconomic status, season of onset, and geographical region in England. To characterise co-occurrence of autoimmune diseases, we calculated incidence rate ratios (IRRs), comparing incidence rates of comorbid autoimmune disease among individuals with a first (index) autoimmune disease with incidence rates in the general population, using negative binomial regression models, adjusted for age and sex. FINDINGS: Among the 22 009 375 individuals included in the study, 978 872 had a new diagnosis of at least one autoimmune disease between Jan 1, 2000, and June 30, 2019 (mean age 54·0 years [SD 21·4]). 625 879 (63·9%) of these diagnosed individuals were female and 352 993 (36·1%) were male. Over the study period, age and sex standardised incidence rates of any autoimmune diseases increased (IRR 2017-19 vs 2000-02 1·04 [95% CI 1·00-1·09]). The largest increases were seen in coeliac disease (2·19 [2·05-2·35]), Sjogren's syndrome (2·09 [1·84-2·37]), and Graves' disease (2·07 [1·92-2·22]); pernicious anaemia (0·79 [0·72-0·86]) and Hashimoto's thyroiditis (0·81 [0·75-0·86]) significantly decreased in incidence. Together, the 19 autoimmune disorders examined affected 10·2% of the population over the study period (1 912 200 [13·1%] women and 668 264 [7·4%] men). A socioeconomic gradient was evident across several diseases, including pernicious anaemia (most vs least deprived area IRR 1·72 [1·64-1·81]), rheumatoid arthritis (1·52 [1·45-1·59]), Graves' disease (1·36 [1·30-1·43]), and systemic lupus erythematosus (1·35 [1·25-1·46]). Seasonal variations were observed for childhood-onset type 1 diabetes (more commonly diagnosed in winter) and vitiligo (more commonly diagnosed in summer), and regional variations were observed for a range of conditions. Autoimmune disorders were commonly associated with each other, particularly Sjögren's syndrome, systemic lupus erythematosus, and systemic sclerosis. Individuals with childhood-onset type 1 diabetes also had significantly higher rates of Addison's disease (IRR 26·5 [95% CI 17·3-40·7]), coeliac disease (28·4 [25·2-32·0]), and thyroid disease (Hashimoto's thyroiditis 13·3 [11·8-14·9] and Graves' disease 6·7 [5·1-8·5]), and multiple sclerosis had a particularly low rate of co-occurrence with other autoimmune diseases. INTERPRETATION: Autoimmune diseases affect approximately one in ten individuals, and their burden continues to increase over time at varying rates across individual diseases. The socioeconomic, seasonal, and regional disparities observed among several autoimmune disorders in our study suggest environmental factors in disease pathogenesis. The inter-relations between autoimmune diseases are commensurate with shared pathogenetic mechanisms or predisposing factors, particularly among connective tissue diseases and among endocrine diseases. FUNDING: Research Foundation Flanders.

Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis. METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

Measurement of the major ignored burden of multiple myeloma, pernicious anaemia and of other haematological conditions on partners and family members: A cross-sectional study.

BACKGROUND: Having a haematological condition can adversely affect the quality of life (QoL) of family members/partners of patients. It is important to measure this often ignored burden in order to implement appropriate supportive interventions. OBJECTIVE: To measure current impact of haematological conditions on the QoL of family members/partners of patients, using the Family Reported Outcome Measure-16 (FROM-16). METHODS: A cross-sectional study, recruited online through patient support groups, involved UK family members/partners of people with haematological conditions completing the FROM-16. RESULTS: 183 family members/partners (mean age = 60.5 years, SD = 13.2; females = 62.8%) of patients (mean age = 64.1, SD = 12.8; females = 46.4%) with 12 haematological conditions completed the FROM-16. The FROM-16 mean total score was 14.0 (SD = 7.2), meaning 'a moderate effect on QoL'. The mean FROM-16 scores of family members of people with multiple myeloma (mean = 15.8, SD = 6.3, n = 99) and other haematological malignancies (mean = 13.9, SD = 7.8, n = 29) were higher than of people with pernicious anaemia (mean = 10.7, SD = 7.5, n = 47) and other non-malignant conditions (mean = 11, SD = 7.4, n = 56, p < .01). Over one third (36.1%, n = 183) of family members experienced a 'very large effect' (FROM-16 score>16) on their quality of life. CONCLUSIONS: Haematological conditions, in particular those of malignant type, impact the QoL of family members/partners of patients. Healthcare professionals can now, using FROM-16, identify those most affected and should consider how to provide appropriate holistic support within routine practice.

Incidence and Predictors of Gastric Neoplastic Lesions in Corpus-Restricted Atrophic Gastritis: A Single-Center Cohort Study.

INTRODUCTION: Corpus-restricted atrophic gastritis is a chronic inflammatory disorder leading to possible development of type 1 neuroendocrine tumors (T1gNET), intraepithelial neoplasia (IEN), and gastric cancer (GC). We aimed to assess occurrence and predictors of gastric neoplastic lesions in patients with corpus-restricted atrophic gastritis at long-term follow-up. METHODS: A prospective single-center cohort of patients with corpus-restricted atrophic gastritis adhering to endoscopic-histological surveillance was considered. Follow-up gastroscopies were scheduled according to the management of epithelial precancerous conditions and lesions of the stomach guidelines. In case of new/worsening of known symptoms, gastroscopy was anticipated. Cox regression analyses and Kaplan-Meier survival curves were obtained. RESULTS: Two hundred seventy-five patients with corpus-restricted atrophic gastritis (72.0% female, median age 61 [23-84] years) were included. At a median follow-up of 5 (1-17) years, the annual incidence rate person-year was 0.5%, 0.6%, 2.8%, and 3.9% for GC/high-grade IEN, low-grade IEN, T1gNET, and all gastric neoplastic lesions, respectively. All patients showed at baseline operative link for gastritis assessment (OLGA)-2, except 2 low-grade (LG) IEN patients and 1 T1gNET patient with OLGA-1. Age older than 60 years (hazard ratio [HR] 4.7), intestinal metaplasia without pseudopyloric metaplasia (HR 4.3), and pernicious anemia (HR 4.3) were associated with higher risk for GC/HG-IEN or LG-IEN development and shorter mean survival time for progression (13.4, 13.2, and 11.1, respectively, vs 14.7 years, P = 0.01). Pernicious anemia was an independent risk factor for T1gNET (HR 2.2) and associated with a shorter mean survival time for progression (11.7 vs 13.6 years, P = 0.04) as well as severe corpus atrophy (12.8 vs 13.6 years, P = 0.03). DISCUSSION: Patients with corpus-restricted atrophic gastritis are at increased risk for GC and T1gNET despite low-risk OLGA scores, and those aged older than 60 years with corpus intestinal metaplasia or pernicious anemia seem to display a high-risk scenario.

A New Case of Association of Megaloblastic Anemia and Pancytopenia of Infants.

BACKGROUND: Vitamin B12, or cobalamin deficiency, an infrequent clinical entity in pediatric age, is found almost solely in breastfed infants whose mothers are purely vegetarian, non-supplemented or with pernicious anemia. Megaloblastic anemia in infants presents with generalized weakness or irritability. METHODS: Diagnosis is usually centered on complete blood count, vitamin dosing, and peripheral smear, which may show macrocytes, hypersegmented neutrophils, reticulocytopenia and a raised mean corpuscular volume (MCV ˃ 100 fL). Pancytopenia has also been noted. RESULTS: We report an exclusive breastfed nine-month-old female child who presented with irritability, developmental delay, and difficulties in introducing new foods. Her initial blood count revealed pancytopenia. Vitamin B12 levels were found to be reduced. Maternal levels of Vitamin B12 were also found to be borderline low. The child was treated as per protocols, and improvement was evidenced with the return of hematological parameters to the regular and gradual advancement of milestones. CONCLUSIONS: We aim to underscore the importance of megaloblastic anemia as an important and rare cause of anemia in infancy.

Endoplasmic Reticulum Stress in the Pathogenesis of Hyperglycemia Induced by Thiamine-Responsive Megaloblastic Anemia.

BACKGROUND: Thiamine responsive megaloblastic anemia (TRMA) is a genetic disease caused by SLC19A2 gene mutation. This study aimed to preliminarily explore the relationship between endoplasmic reticulum stress (ERS)-PERK signaling pathway and the pathogenesis of hyperglycemia induced by TRMA. METHODS: Islet ß (INS.1 and ß-TC-6) and HEK293T cell line models with stable overexpression of SLC19A2 and SLC19A2 (c.1409insT) were established. The cells were divided into empty virus group (control), wild-type group (overexpressed SLC19A2), and mutation group (overexpressed SLC19A2 (c.1409insT)). Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of ERS-PERK signaling pathway-related proteins, including glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK), and eukaryotic initiation factor 2 (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in islet ß cells. Protein localization was assessed by immunofluorescence staining. RESULTS: Compared with the control group, the mRNA expression levels of SLC19A2 in wild-type and mutant islet ß cells (INS.1 and ß-TC-6) and HEK293T cells were significantly upregulated (all p < 0.05). Compared with the control group and the wild-type group, the mRNA expression levels of GRP78, PERK, eIF2α, ATF4, and CHOP were increased (all p < 0.05) in the mutant islet ß cells; the protein expression levels of PERK, GRP78, and eIF2α were elevated (all p < 0.05). In addition, the results of immunofluorescence staining showed that SLC19A2 (c.1409insT) mutation changed the localization of the proteins in the cells. Thus, they were not located on the cell surface, but in the cytoplasm and nuclei, and protein aggregation occurred in the cytoplasm. CONCLUSIONS: 1. Islet ß and HEK293Tcell lines, stably overexpressing SLC19A2 and SLC19A2 (c.1409insT) mutations, were successfully constructed. 2. SLC19A2 (c.1409insT) mutation could raise the expression levels of ERS-PERK signaling pathway-related proteins (GRP78, PERK, eIF2α, ATF4, and CHOP), and activate apoptosis pathway. 3. SLC19A2 (c.1409insT) mutation could change the localization of proteins and produce protein aggregation in cells. It could lead to protein misfolding and ERS, which would participate in the pathological mechanism of hyperglycemia induced by TRMA.

Primary Neurologic Symptoms: Have You Considered Pernicious Anemia?

BACKGROUND: Vitamin B12, or cobalamin, is a nutrient that is vital for metabolic function. Absorption of ingested B12 is dependent on intrinsic factor, which is secreted by parietal cells within the stomach. Pernicious anemia is caused by an intrinsic factor deficiency or autoantibodies against intrinsic factor. The presence of parietal cell antibodies can destroy parietal cells, which can also lead to a deficiency in intrinsic factor. Both lead to megaloblastic anemia caused by vitamin B12 deficiency. The typical presentation of pernicious anemia includes fatigue, pale appearance, tingling sensation, depression, alterations to vision and smell, urinary incontinence, psychotic episodes, and weakness. The most effective treatment for pernicious anemia is intramuscular B12. CASE REPORT: A 27-year-old woman with a history of vitiligo presented to the emergency department (ED) with bilateral lower extremity weakness, clumsiness, numbness, and tingling. Physical examination revealed ataxia, no sensation below her umbilicus, decreased strength, and hyperreflexia in both lower extremities. Complete blood count in the ED revealed low hemoglobin and hematocrit and elevated mean corpuscular volume, concerning for pernicious anemia. Further laboratory testing upon inpatient admission revealed a low vitamin B12 level and parietal cell antibodies in the blood. The patient's pernicious anemia was treated with intramuscular vitamin B12 injections, which led to near complete resolution of her symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Early suspicion and detection of pernicious anemia in the ED can prevent serious and permanent hematologic and neurologic damage and the development of other autoimmune disorders.

Atopic dermatitis and risk of autoimmune conditions: Population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is associated with immune dysregulation, but epidemiologic data on the pattern of autoimmune comorbidity in people with AD are limited. OBJECTIVE: We sought to determine the risk of autoimmune conditions in people newly diagnosed with AD. METHODS: Retrospective cohort analysis (January 2009 to December 2018), using the UK-based Oxford-Royal College of General Practitioners Research and Surveillance Centre primary care database. We compared baseline prevalence and incidence after diagnosis of autoimmune conditions in 173,709 children and adults with new-onset AD and 694,836 age-, sex-, and general practitioner practice-matched controls. Outcomes were a composite of any autoimmune condition (Crohn disease, ulcerative colitis, celiac disease, pernicious anemia, type 1 diabetes, autoimmune hypothyroidism, Graves disease, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, Sjögren syndrome, vitiligo, alopecia areata, and multiple sclerosis) and each individual autoimmune condition. RESULTS: Preexisting autoimmune conditions were more common in people diagnosed with AD compared to controls (composite 5.8% vs 4.3%). Excluding people with preexisting autoimmune disease, there was an association between AD and incidence of new-onset autoimmune disease (composite adjusted hazard ratio [aHR] 1.28; 95% confidence interval [CI] 1.23-1.34). Risk was highest for more severe AD (aHR 1.99; 95% CI 1.77-2.23) than moderate AD (aHR 1.33; 95% CI 1.19-1.49) or mild AD (aHR 1.22; 95% CI 1.16-1.28). People with AD were at significantly increased risk of developing psoriatic arthritis, Sjögren syndrome, Crohn disease, vitiligo, alopecia areata, pernicious anemia, ulcerative colitis, rheumatoid arthritis, and hypothyroidism (aHR range 1.17-2.06), but not other autoimmune conditions. CONCLUSION: People with AD have an increased risk of multiple autoimmune conditions, especially those with more severe AD.

[Apathetic state of mind due to pernicious anemia]. / Apathische gemoedstoestand ten gevolge van een pernicieuze anemie.

In this case study we describe a man who came to a mental health care centre (MHCC) with difficult to interpret complaints such as loss of fear and empathy, apathy and cognitive symptoms. In addition, he experienced a pronounced fatigue. Later he suffered from cold extremities, bilateral hypoesthesia of the hands and paresthesias of the legs. Routine laboratory tests initially showed no abnormalities. Only later a decreased hemoglobin and vitamin B12 value was seen in the context of a pernicious anemia. A treatment with vitamin B12 supplementation was started, after which gradual improvement of the symptoms was seen. This case study shows that vitamin B12 deficiency can result in both psychiatric and cognitive symptoms including memory and attention problems. The initial presentation of pernicious anemia can involve only psychiatric symptoms before neurological and hematological symptoms are present and before anemia is objectively diagnosed.

Associations Between Autoimmune Conditions and Gastric Cancer Risk Among Elderly Adults in the United States.

INTRODUCTION: Pernicious anemia (PA) is a risk factor for gastric cancer. Other autoimmune conditions may also contribute. METHODS: In a case-control study, we evaluated 47 autoimmune conditions among 39,125 gastric cancers and 200,000 cancer-free controls. RESULTS: Six conditions were associated with increased gastric cancer risk (range of adjusted odds ratios: 1.28-1.93, P < 0.05): PA, membranous nephropathy, primary biliary cirrhosis, pure red cell aplasia, primary sclerosing cholangitis, and Graves disease. PA was associated with 8 other autoimmune conditions (adjusted odds ratios: 1.57-4.54, P < 0.05). DISCUSSION: Autoimmune conditions associated with gastric cancer or PA may reflect effects of autoimmune gastritis or other carcinogenic pathways.

Aggregation of autoimmunity in extended families of people with autoimmune Addison disease.

BACKGROUND: Autoimmunity accounts for 90% of cases of primary adrenal insufficiency (Addison disease (AD)). Affected people present a significant co-occurrence of autoimmune conditions; hence, clustering of autoimmunity is also predicted among their relatives. AIMS: To evaluate the burden of autoimmunity in families of people with AD. METHODS: A total of 116 individuals with AD was surveyed regarding the occurrence of 23 autoimmune diseases among their relatives. RESULTS: A total of 74.1% of persons with AD reported at least one relative with an autoimmune disorder - 257 cases were diagnosed in 221 relatives. Hashimoto thyroiditis was found in 100 individuals, followed by Graves disease and vitiligo, in 25 and 24 relatives respectively. Type 1 diabetes was diagnosed in 23 relatives, psoriasis in 15, rheumatoid arthritis in 12, pernicious anaemia in 11, multiple sclerosis in 8, and premature menopause in 8 women. AD was found in seven relatives, alopecia in six and celiac disease in five. Other conditions were rare. Significant correlation was noticed between the number of autoimmune conditions in AD proband and the number of affected relatives (P = 0.031). A total of 66.4% of people with AD had a first-degree relative suffering from autoimmunity. Autoimmune conditions were more frequent among females: sisters (P < 0.001), mothers (P = 0.002) and grandmothers (P = 0.002). CONCLUSIONS: Considerable prevalence of autoimmune conditions in relatives of people with AD confirms substantial risk of autoimmunity, especially in females and relatives of patients affected by multiplex autoimmunity. Our data corroborate the recommendation of active screening for autoimmune disorders, particularly thyroid disease, among AD family members.

Genetically predicted circulating B vitamins in relation to digestive system cancers.

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 (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 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 ORSD 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.

A patient and public involvement workshop using visual art and priority setting to provide patients with a voice to describe quality and safety concerns: Vitamin B12 deficiency and pernicious anaemia.

BACKGROUND: Patient and public involvement and engagement (PPIE) is recognized as important for improved quality in health service provision and research. Vitamin B12 deficiency is one area where PPIE has potential to benefit patients, as patients often report sub-optimal care due to diagnostic delay, insufficient treatment and poor relationships with health professionals. OBJECTIVE: In an effort to engage an understudied patient population in health-care quality and safety discussions, and provide patients with an opportunity to have a voice, contribute to research priorities and express their current quality and safety concerns, we hosted a PPIE workshop. METHODS: One researcher (with lived experience) facilitated a one day workshop with 12 patients with varied demographics. The workshop had four components (a) one-to-one sessions with an artist, (b) quality and safety research/education priority setting, (c) comments on research proposals, and (d) development of a PPIE group for future research. RESULTS: All elements of the workshop elicited a number of quality and safety priorities for the group. Priority setting highlighted issues with interpretation of test results, symptom-based treatment, self-medication and relationship with primary care health-care professionals. One of the major safety issues highlighted in the visual art element was feeling ignored, silenced or not listened too by health-care professionals. DISCUSSION: Visual art methods to express experiences of health, and research priority setting tasks achieved the aim of providing patients with an opportunity to have a voice and express concerns about health-care quality and safety issues. The addition of visual art allowed patients to articulate emotions and impacts on everyday life associated with quality and safety. PATIENT OR PUBLIC CONTRIBUTION: A public contributor was involved in preparation of this manuscript. The event aimed to enable PPIE contribution in future research.

Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene-a case report.

BACKGROUND: Hereditary intrinsic factor deficiency is a rare disease characterized by cobalamin deficiency with the lack of gastric intrinsic factor because of gastric intrinsic factor (GIF) mutations. Patients usually present with cobalamin deficiency without gastroscopy abnormality and intrinsic factor antibodies. CASE PRESENTATION: A Chinese patient presented with recurrent severe anemia since age 2 with low cobalamin level and a mild elevation of indirect bilirubin. The hemoglobin level normalized each time after intramuscular vitamin B12 injection. Gene test verified a c.776delA frame shift mutation in exon 6 combined with c.585C > A nonsense early termination mutation in exon 5 of GIF which result in the dysfunction of gastric intrinsic factor protein. The hereditary intrinsic factor deficiency in literature was further reviewed and the ancestry of different mutation sites were discussed. CONCLUSIONS: A novel compound heterozygous mutation of GIF in a Chinese patient of hereditary intrinsic factor deficiency was reported. It was the first identified mutation of GIF in East-Asia and may indicate a new ancestry.

Nutritional neuropathies.

Neuropathies associated with nutritional deficiencies are routinely encountered by the practicing neurologist. Although these neuropathies assume different patterns, most are length-dependent, sensory axonopathies. Cobalamin deficiency neuropathy is the exception, often presenting with a non-length-dependent sensory neuropathy. Patients with cobalamin and copper deficiency neuropathy characteristically have concomitant myelopathy, whereas vitamin E deficiency is uniquely associated with a spinocerebellar syndrome. In contrast to those nutrients for which deficiencies produce neuropathies, pyridoxine toxicity results in a non-length-dependent sensory neuronopathy. Deficiencies occur in the context of malnutrition, malabsorption, increased nutrient loss (such as with dialysis), autoimmune conditions such as pernicious anemia, and with certain drugs that inhibit nutrient absorption. When promptly identified, therapeutic nutrient supplementation may result in stabilization or improvement of these neuropathies.

Role of Pernicious Anemia in Patients Admitted to Internal Medicine with Vitamin B12 Deficiency and Oral Replacement Therapy as a Treatment Option.

BACKGROUND: To determine the role of vitamin B12 deficiency in pernicious anemia and the efficacy of oral vitamin B12 replacement therapy given regardless of the etiology, and to compare the endoscopic and pathological findings in patients diagnosed with vitamin B12 deficiency. METHODS: The study included 216 patients, aged 18 - 65 years, diagnosed with vitamin B12 level < 200 pg/mL between May 2015 and May 2016. Evaluation was made of the demographic characteristics of the patients, diseases, drugs used, dietary habits, previous use of vitamin B12 replacement therapy, family history of vitamin B12 deficiency, laboratory test values, and neurological symptoms present at the time of presentation. Endoscopy was applied to all the patients included in the study. Anti-parietal cell antibody (APCA) and anti-intrinsic factor antibody (AIFA) analyses were applied to all patients. RESULTS: Evaluation was made of a total of 216 patients diagnosed with vitamin B12 deficiency, comprising 145 (67.1%) females and 71 (32.9%) males. The mean vitamin B12 level of the patients was determined as 127 pg/mL at the time of presentation and 334 pg/mL after treatment. APCA positivity was determined in 40 (18.5%) patients, and AIFA positivity in 5 (2.3%) patients. Atrophy was determined endoscopically in 53 (24.5%) patients and pathologically in 90 (41.7%). Helicobacter pylori positivity was determined in 196 (90.7%) patients. A diagnosis of pernicious anemia (PA) was made in 4 (1.9%) patients (patients with AIFA positivity or APCA accompanied by corpus atrophy). APCA positivity was determined but not corpus atrophy in 36 (16.7%) patients and these cases were accepted as suspected pernicious anemia. In this study of 216 patients with vitamin B12 deficiency, stomach pathologies which could cause vitamin B12 deficiency (atrophic gastritis, HP, PA) and the responses to oral replacement therapy were investigated. As vitamin B12 absorption plays a role in the pathogenesis. Vitamin B12 deficiency can lead to atrophic gastritis, and this was determined with biopsy in 41.7% of the patients. APCA positivity was determined in 18.5% of the patients investigated with respect to autoimmune atrophic gastritis (pernicious anemia) and AIFA positivity in 2.3%. A diagnosis of PA was made in 4 (1.9%) patients from autoimmune marker positivity and the presence of corpus atrophic gastritis. HP was determined in 90.7% of the patients with vitamin B12 deficiency, and although no correlation was determined between HP and atrophy, HP positivity was determined in 84 (93.3%) of the patients with pathological atrophy. From the time of diagnosis, the patients in the study were prescribed 1,000 µg/day vitamin B12. At the 40-day follow-up examination, a significant increase was observed in the vitamin B12 levels of 92.5% of the patients. At the end of the study, as oral replacement therapy was seen to be effective to a great extent, even in patients with PA, it was concluded that for patients not responding to oral replacement therapy, it would be appropriate to apply parenteral vitamin B12 treatment. CONCLUSIONS: In developing countries such as Turkey, the role of HP infection in vitamin B12 deficiency must be kept in mind. The incidence of atrophic gastritis and pernicious anemia is higher than expected in vitamin B12 deficiency. Thus, it can be concluded that it is appropriate to investigate patients with vitamin B12 deficiency with respect to atrophic gastritis and PA, and oral replacement therapy should be the first stage in the treatment of vitamin B12 deficiency.

Anemia, hematinic deficiencies, hyperhomocysteinemia, and gastric parietal cell antibody positivity in atrophic glossitis patients with iron deficiency.

BACKGROUND/PURPOSE: Our previous study found that 180 of 1064 atrophic glossitis (AG) patients have iron deficiency. This study assessed whether all AG patients with iron deficiency (so-called ID/AG patients) had iron deficiency anemia (IDA) and evaluated whether the ID/AG patients had significantly higher frequencies of anemia, hematinic deficiencies, hyperhomocysteinemia, and serum gastric parietal cell antibody (GPCA) positivity than healthy control subjects. METHODS: The blood hemoglobin (Hb) and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels in 180 ID/AG patients and 532 healthy control subjects were measured and compared. RESULTS: We found that 180 ID/AG patients had significantly lower mean corpuscular volume (MCV) and lower mean blood Hb and serum iron levels as well as significantly higher mean serum homocysteine level than healthy control subjects (all P-values < 0.001). Moreover, 180 ID/AG patients had significantly higher frequencies of blood Hb (46.1%), serum iron (100.0%), vitamin B12 (8.3%), and folic acid (4.4%) deficiencies, hyperhomocysteinemia (16.1%), and serum GPCA positivity (31.1%) than 532 healthy control subjects (all P-values < 0.001). In addition, of 83 anemic ID/AG patients, 9 (10.8%) had pernicious anemia, 40 (48.2%) had normocytic anemia, 30 (36.2%) had IDA, and 4 (4.8%) had thalassemia trait-induced anemia. CONCLUSION: We conclude that ID/AG patients had significantly higher frequencies of blood Hb, serum iron, vitamin B12, and folic acid deficiencies, hyperhomocysteinemia, and serum GPCA positivity than 532 healthy control subjects. Normocytic anemia is the most common type of anemia in ID/AG patients, followed by IDA, pernicious anemia, and thalassemia trait-induced anemia.

[Cancer or vitamin B12 deficiency? Difficult differential diagnosis in elderly]. / Nowotwór czy niedobór witaminy B12? Trudna diagnostyka róznicowa u osób starszych.

Vitamin B12 deficiency anaemia in adults is usually caused by Addison- Biermer's disease. The presence of antibodies against gastric parietal cells and intrinsic factor (IF) in blood is typical for the disease. The gastrointestinal malabsorption or a diet poor in vitamin B12 are rarer causes. The disease manifests in hematological, neurological, psychiatric disorders and trophic changes of the tongue and oral mucosa, which leads to weight loss. A CASE REPORT: The authors describe a case of a 70-year-old woman with severe vitamin B12 deficiency based on chronic inflammatory lesions of the gastric mucosa caused by Helicobacter pylori infection. The patient had haematological (pancytopenia), neurological (problems with memory, concentration, numbness of the limbs, gait instability) and gastrological disorders (loss of appetite, weight loss). The laboratory and imaging diagnostics were performed. The neoplasmatic background was abandoned and pure vitamin B12 deficiency was diagnosed. All symptoms resolved completely after the supplementation and eradication of Helicobacter pylori. CONCLUSIONS: The article demonstrates the problem of many severe, non- specific complications of vitamin B12 deficiency which requires extensive diagnostics and treatment. The similarity of symptoms may suggest a malignant disease especially in elderly patients.