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.

Retrospective cross-sectional study of 34 cases of pernicious anemia at Mohammed V Military Training Hospital, Morocco.

Introduction: pernicious anemia is an autoimmune disease characterized by atrophic gastritis due to malabsorption of vitamin B12. Certain oral manifestations, such as Hunter´s glossitis and burning mouth syndrome, may precede the onset of this anemia. The aim of this study is to describe the clinical presentation, para-clinical aspects, the treatment, and the evolution of the pernicious anemia (PA) after treatment. Methods: retrospective study conducted at the Department of Haematology and Internal Medicine B of the Mohammed V Military Training Hospital in Rabat between January 2009 and December 2018. Thirty-four patients were enrolled with vitamin B12 deficiency, non-regenerative macrocytic anemia, a positive anti-intrinsic factor antibody and anti-parietal cell antibody and a histological diagnosis of atrophic gastritis in the presence or not of Helicobacter pylori. The qualitative variables were expressed in numbers and percentages, and the quantitative variables in mean and standard deviation. Multivariate analysis used the Fischer test; it was considered significant for a p < 0.05 value. Results: thirty-four cases were studied; the population study consists of 56% (n=19) of men and 44% (n=15) of women. The average age was 54.88± 9.14. The clinical manifestations of pernicious anemia are dominated by megaloblastic anemia 85.3% (n=29), followed by digestive 58.8%(n=20) and oral 55.9% (n=19) signs. Neurological manifestations were rarely found in 41% (n=14). Hunter´s glossitis 37% (n=7), stomatodynia 11% (n=2) were the most common oral manifestations accompanying pernicious anemia. The evolution was favorable in 79.4% (n=27) patients under substitution therapy with vitamin B12. Conclusion: dentists´ involvement in the diagnosis of pernicious anemia is based on changes in oral mucous membranes, which have been reported in 55.9% of all patients. These oral changes may occur in the absence of symptomatic anemia.

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.

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.

Gastric cancer in autoimmune gastritis: A case-control study from the German centers of the staR project on gastric cancer research.

OBJECTIVES: Patients with autoimmune gastritis (AIG) are reported to have an increased risk of developing gastric cancer (GC). In this study, we assess the characteristics and outcomes of GC patients with AIG in a multicenter case-control study. METHODS: Between April 2013 and May 2017, patients with GC, including cancers of the esophagogastric junction (EGJ) Siewert type II and III, were recruited. Patients with histological characteristics of AIG were identified and matched in a 1:2 fashion for age and gender to GC patients with no AIG. Presenting symptoms were documented using a self-administered questionnaire. RESULTS: Histological assessment of gastric mucosa was available for 572/759 GC patients. Overall, 28 (4.9%) of GC patients had AIG (67 ± 9 years, female-to-male ratio 1.3:1). In patients with AIG, GC was more likely to be localized in the proximal (i.e. EGJ, fundus, corpus) stomach (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.0-7.1). In GC patients with AIG, pernicious anemia was the leading clinical sign (OR 22.0, 95% CI 2.6-187.2), and the most common indication for esophagogastroduodenoscopy (OR 29.0, 95% CI 7.2-116.4). GC patients with AIG were more likely to present without distant metastases (OR 6.2, 95% CI 1.3-28.8) and to be treated with curative intention (OR 3.0, 95% CI 1.0-9.0). The five-year survival rates with 95% CI in GC patients with and with no AIG were 84.7% (83.8-85.6) and 53.5% (50.9-56.1), respectively (OR 0.25, 95% CI 0.08-0.75, p = 0.001). CONCLUSIONS: Pernicious anemia leads to earlier diagnosis of GC in AIG patients and contributes significantly to a better clinical outcome.

Predictive risk factors for autoimmune thyroid diseases in patients with pernicious anemia.

BACKGROUND: Patients with pernicious anemia (PA) have a higher prevalence of other autoimmune diseases. We assessed the correlation between PA and autoimmune thyroid diseases (AITD), and evaluated the risk factors for this association. METHODS: A longitudinal study was conducted involving patients with PA between 2010 and 2017. RESULTS: A total of 86 patients with PA were evaluated, 74 (86%) female, with a median age of 51.5 years. Thyroid abnormalities were detected in 45 (52.3%) patients, including 28 (32.3%) hypothyroidism, 3 (3.5%) hyperthyroidism and 20 (23.3%) thyroperoxidase antibody positivity. Logistic regression analysis identified risk factors for having AITD in PA patients: weight loss (OR 12.03; 95% CI 1.06-137.02, P=0.045), diabetes mellitus (OR 4.68, 95% CI 1.15-26.58, P=0.047) and gastric antibodies positivity (OR 5.05, 95% CI 1.45-18.24, P=0.013). CONCLUSION: PA and AITD are frequently associated, suggesting all patients with PA should be investigated for occult thyroid disease, especially those with weight loss, diabetes mellitus and gastric autoantibodies.

[Neurological disorders secondary to vitamin B12 deficiency: about 29 cases]. / Les troubles neurologiques secondaires à une carence en vitamine B12: analyse de 29 cas.

Neurological disorders secondary to vitamin B12 deficiency are polymorphic and diverse. There have been very few studies conducted in the Moroccan as well as in the African population. This study aims to describe the clinical, paraclinical, evolutionary features of neurological manifestations in patients with vitamin B12 deficiency within the Department of Neurology at the Moulay Ismail Military Hospital, Meknes over a period of 18 years (1999-2017). The study involved 06 women and 23 men, with an average age of 57 years. The mean time between symptom onset and diagnosis was 3 months. Neurological manifestation was indicative of vitamin B12 deficiency in 100% of cases. The average hemoglobin level was 10 g/dl, the mean corpuscular volume was 115 fl. Medullary megaloblastosis and atrophic gastritis were found in 95% and 90% of cases respectively. Regular electromyography (EMG), electroencephalography (EEG) and visual evoked potentials (VEP) showed subclinical peripheral and optic neuropathies. In 20 cases they were caused by Biermer's anemia. All the patients received parenteral Vitamin B12 with good outcome. These results demonstrate the importance of early diagnosis in patients with a potentially serious neuropsychiatric condition as well as of rapid substitution treatment which is the only therapeutic option to secure a good outcome.

Parallel transverse uterine incisions combined with cell salvage minimized bleeding in a patient with pernicious placenta previa and an unexplained decrease in hemoglobin after transfusion of allogeneic red blood cells: A case report.

RATIONALE: The incidence of pernicious placenta previa (PPP) and placenta accreta (PA) is increasing in China. Excessive blood loss in these women is an important cause of maternal death and emergency hysterectomy. Performing a traditional cesarean section (CS) in women with PPP is stressful for obstetricians because avoiding cutting the placenta is difficult. As a result, sudden life-threatening bleeding may be encountered. Therefore, there is an urgent need to establish a novel operative method for PPP and PA that is safe for both the mother and neonate, and less stressful for the surgeon. PATIENT CONCERNS: We report an extremely rare case of PPP and PA complicated with anemia and an unexplained decrease in the hemoglobin (Hb) levels after transfusion of 3 units of allogeneic red blood cells. DIAGNOSES: The patient was diagnosed with unexplained anemia, and hemolysis resulting from donor red blood cell transfusion was suspected preoperatively. INTERVENTIONS: To minimize blood loss for safety, a new operative technique, parallel transverse uterine incisions (PTUI) in CS (PTUI CS), was used under general anesthesia in this case. Inhaled volatile sevoflurane was used for uterine relaxation during PTUI. Cell salvage was also used. OUTCOMES: PTUI CS combined with cell salvage effectively reduced bleeding and preserved the uterus in our patient. Sevoflurane was effective for uterine relaxation during PTUI CS. LESSONS: If PPP and PA are suspected, placental magnetic resonance imaging is recommended for definitively determining whether a transverse fundal incision can be made. If feasible, we strongly recommend that PTUI CS combined with cell salvage are used to minimize bleeding for high-risk patients with PPP and PA complicated with anemia and an unexplained decrease in Hb levels after transfusion of 3 units of allogeneic red blood cells. Anesthesiologists should be vigilant to maintain uterine relaxation from the time of delivery of the neonate to a second transverse incision in the lower segment of the uterus. This is a key element of successful PTUI CS. Additionally, the use of intraoperative cell salvage is recommended when it can be expected to reduce the likelihood of donor red cell transfusion.

Helicobacter pylori infection and nonmalignant diseases.

A substantial decrease in Helicobacter pylori-associated peptic ulcer disease has been observed during the last decades. Drug-related ulcers as well as idiopathic ulcers are becoming predominant and are more refractory to treatment; however, H. pylori infection still plays an important role in ulcer bleeding and recurrence after therapy. The effect of H. pylori eradication upon functional dyspepsia symptoms has been reviewed in this article and generally confirms the results of previous meta-analyses. Additional evidence suggests a lack of impact upon the quality of life, in spite of improvement in symptoms. The association of H. pylori with gastroesophageal reflux disease and Barrett's esophagus remains controversial with a majority of published studies showing a negative association. Furthermore, a strong inverse relationship between the presence of H. pylori and the esophageal eosinophilia was also reported. Several studies and a review addressed the role of H. pylori in autoimmune gastritis and pernicious anemia. The association of the above still remains controversial. Finally, the necessity of routine endoscopy and H. pylori eradication before bariatric surgery is discussed. Several studies suggest the rationale of preoperative upper endoscopy and H. pylori eradication prior to surgery. However, the prevalence of H. pylori infection prior to surgery in these studies generally reflects the overall prevalence of the infection in the particular geographic area. In addition, results on the role of H. pylori in developing postoperative complications remain controversial.

Autoimmune gastritis: relationships with anemia and Helicobacter pylori status.

BACKGROUND: Autoimmune gastritis (AIG) is a gastric pathologic condition affecting the mucosa of the fundus and the body and eventually leading to hypo-achlorhydria. AIMS: We report our clinical and pathological experience with AIG. METHODS: Data from patients with a diagnosis of AIG seen in the period January 2002-December 2012 were retrieved. Only patients with complete sets of biopsies were analyzed. RESULTS: Data from 138 patients were available for analysis. Pernicious anemia was present in 25% of patients, iron deficiency anemia was found in 29.7% of patients, hypothyroidism in 23% of patients, type 1 diabetes in 7.9% of patients, and vitiligo in 2.8% of patients. Parietal cell antibodies were positive in 65% of patients, and no patient had serology positive for celiac disease. All gastric biopsies showed glandular atrophy associated with enterochromaffin-like (ECL)-cells hyperplasia, features limited to the mucosa of the fundus and body, and focal glandular intestinal metaplasia. Helicobacter pylori was negative in all cases. CONCLUSIONS: AIG was strongly associated with anemia; atrophy, intestinal metaplasia and ECL hyperplasia in the gastric fundus and body are hallmarks of this condition.

Quality of Life, Burden of Disease, Co-morbidities, and Systemic Effects in Vitiligo Patients.

Vitiligo is a complex, systemic disease associated with many autoimmune and autoinflammatory conditions. Additionally, the cutaneous changes of vitiligo have significant effects on quality of life and self-esteem. Further efforts are needed to increase our understanding of vitiligo comorbidities as well as to increase awareness of the psychological effects of vitiligo.

Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis.

BACKGROUND: Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. CONCLUSION: Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA.

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study.

OBJECTIVE: To investigate the association between pernicious anemia and other autoimmune diseases. METHODS: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. RESULTS: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. CONCLUSION: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

Pernicious anemia and colorectal cancer risk - A nested case-control study.

BACKGROUND: Hypergastrinemia was shown to stimulate colonic epithelial cell proliferation. AIMS: To evaluate the association between pernicious anemia (PA), a disease with hypergastrinemia, and colorectal cancer (CRC) risk. METHODS: We conducted a nested case-control study within a large database from the UK. Cases were defined as all individuals in the cohort with at least one medical code for CRC. Controls were selected based on incidence-density sampling. For each case, up to four eligible controls were matched on age at diagnosis, sex, practice-site, and both duration and calendar time of follow-up. Exposure of interest was diagnosis of PA prior to CRC diagnosis date. The primary analysis was a multivariable conditional logistic regression. RESULTS: Our study included 22,098 CRC cases and 85,969 matched controls. We identified 154 (0.70%) cases and 563 (0.65%) controls with past history of PA. The adjusted OR for the association between PA and CRC risk was 1.02 (95% CI 0.85-1.22). There was no difference in the results after stratification according to sex. In a sensitivity analysis only among individuals without chronic use of proton pump inhibitors (PPIs) the adjusted OR was 1.14 (95% CI 0.90-1.45). There was no association between duration of PA and CRC risk. CONCLUSION: PA is not associated with higher CRC risk.

Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study.

BACKGROUND: Few large-scale studies have quantified the burden of comorbid autoimmune diseases in patients with vitiligo. OBJECTIVE: We sought to determine the prevalence of comorbid autoimmune diseases in patients with vitiligo. METHODS: We conducted a manual chart review on a cohort of 1873 patients with vitiligo seen between January 2002 and October 2012 at the Henry Ford Health System in Detroit, MI. Patients were excluded if they had fewer than 2 dermatology notes (N = 595) or if they were never given a diagnosis of vitiligo by a dermatologist (N = 180). RESULTS: Of 1098 patients with vitiligo, nearly 20% had at least 1 comorbid autoimmune disease. Compared with the general US population, we found a higher prevalence of thyroid disease (12.9%, P < .001), alopecia areata (3.8%, P < .001), inflammatory bowel disease (0.9%, P = .046), pernicious anemia (0.5%, P = .007), systemic lupus erythematosus (0.3%, P = .048), Guillain-Barre syndrome (0.3%, P < .001), discoid lupus (0.2%, P = .003), linear morphea (0.2%, P < .001), myasthenia gravis (0.2%, P = .002), and Sjögren syndrome (0.2%, P = .011). LIMITATIONS: The study lacked a control group. This was a single-institution study with possible selection bias, and thus the findings may not be representative of the overall population of patients with vitiligo. CONCLUSIONS: We observed a high prevalence of comorbid autoimmune diseases in patients with vitiligo and report several new associations.

Risk of community-acquired pneumonia in patients with a diagnosis of pernicious anemia: a population-based retrospective cohort study.

OBJECTIVE: Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at an increased risk for community-acquired pneumonia (CAP). METHODS: We performed a retrospective cohort study using The Health Improvement Network (THIN) from the UK (1993-2009). The eligible study cohort included individuals 18 years of age or older, with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio with the 95% confidence interval for CAP associated with PA, accounting for a comprehensive list of potential confounders. RESULTS: The study included 13,605 individuals with PA and 50,586 non-PA individuals. The crude incidence rate of CAP was 9.4/1000 person-years for those with PA, versus 6.4/1000 person-years for those without PA. The multivariable adjusted hazard ratio for CAP associated with PA was 1.18 (95% confidence interval 1.08-1.29). CONCLUSION: In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at an increased risk for CAP.

Autoimmune mechanisms in pernicious anaemia & thyroid disease.

Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels.