Pernicious anemia is a common cause of cobalamin deficiency-caused megaloblastic anemia in Hainan, China.

BACKGROUND: Pernicious anemia (PA) is believed to be highly prevalent in Western countries but has rarely been reported in China. The study explores whether PA, an autoimmune disease, is an uncommon cause of cobalamin (vitamin B12) deficiency anemia in China. METHODS: Clinical and hematological data were collected from 90 cobalamin deficiency-caused megaloblastic anemia (MA) patients between July 2014 and December 2021. Through anti-intrinsic factor antibody (IFA) and anti-parietal cell antibody (PCA) testing, PA was distinguished from other causes of cobalamin deficiency leading to MA. Meanwhile, 30 healthy controls (HCs) were included to estimate the positive rates of IFA and PCA. RESULTS: Of the 30 HCs, only one tested positive for IFA, and all 30 tested negative for PCA. Among the 90 patients with cobalamin deficiency-caused MA, 76.7% were positive for IFA, and 47.8% were positive for PCA; a total of 76 patients (84.4%) were diagnosed with PA. The mean follow-up time was 41.0 ± 16.3 months. During the follow-up period, no case relapsed among the continuous cobalamin-supply treatment patients, while 24.4% of patients relapsed due to the interruption of maintenance cobalamin-supplement therapy (the median recurrence time was 54.0 ± 17.7 months). CONCLUSIONS: The proportion of PA in cobalamin deficiency-caused MA patients in Hainan province was higher than 80%, which was more common than expected. Therefore, screening for IFA, PCA, endoscopic biopsy, and thyroid-related parameters are recommended for all cobalamin deficiency-caused MA patients. Furthermore, maintenance cobalamin-supplement therapy is important for PA patients.

This research examines pernicious anemia (PA), a type of anemia caused by vitamin B12 deficiency, which has been widely reported in Western countries but is less known in China. The study focuses on determining if PA is also a significant cause of this deficiency in Hainan, China. Researchers gathered data from patients with megaloblastic anemia (a blood disorder) due to lack of vitamin B12, comparing them with healthy individuals to see how common PA is. The findings reveal that a very high percentage of the patients studied have PA, much higher than expected. This suggests that PA is not as rare in this region of China as previously thought. The study also highlights the importance of continuous treatment with vitamin B12 to prevent the recurrence of the anemia. Based on these results, the researchers recommend that all patients with vitamin B12 deficiency should be tested for PA and continuously receive vitamin B12 supplements to maintain their health once diagnosed with PA. This strategic insight is of paramount importance to medical practitioners in China, potentially paving the way for enhanced clinical management protocols for individuals afflicted by this ailment.

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.

Antibodies involved in the development of pernicious anemia and other autoimmune diseases.

INTRODUCTION: Pernicious anemia (PA) is an autoimmune hematopoietic disease. OBJECTIVES: The aim of the study was to determine autoantibodies involved in the pathogenesis of PA and the development of other autoimmune disorders such as connective tissue diseases and celiac disease. We also aimed to assess the potential usefulness of the specific diagnostic and screening tests in patients with PA. PATIENTS AND METHODS: The study group comprised 124 women and men with newly diagnosed PA and 41 healthy controls. Intrinsic factor (IF) antibodies, gastric parietal cell (GPC) antibodies, endomysium antibodies (EmAs), and antinuclear antibodies (ANAs) were determined in blood samples. RESULTS: IF or GPC antibodies were present in 61.3% of patients, GPC antibodies, in 46%, IF antibodies, in 30.6%, IF and GPC antibodies, in 15.3%. There was no difference in the occurrence of ANAs and EmAs between the PA and control groups. However, ANAs were found in 16.1% of patients with PA and in 4.9% of controls. The occurrence of EmAs in both groups was similar (3.2% vs 2.4%); however, it has been shown that patients with IF or GPC antibodies are more prone to be EmA positive (P = 0.009). CONCLUSIONS: Simultaneous determination of IF and GPC antibodies increases the chances of confirming the diagnosis of PA. Also, screening for connective tissue diseases and celiac disease may be considered in patients with PA, due to the presence of ANAs and EmAs in that population.

Diagnostic difficulties in pernicious anemia.

Pernicious anemia (PA), the commonest cause of cobalamin deficiency (CD) in the world, is an autoimmune disease of multifactorial origin and is characterized by chronic atrophic gastritis (CAG) and defective absorption of cobalamin from the terminal ileum due to interference by the intrinsic factor (IF) antibodies. PA-related CD is a lengthy process, which if untreated, can lead to irreversible hematological and neurological sequelae. Although safe and effective therapy is available and the management of PA is straightforward, the diagnosis of PA can be extremely difficult to obtain due to myriad and diverse clinical presentations, frequently coexisting diseases, and limitations of currently available diagnostic tests. Diagnostic dilemmas may occur when PA patients present with normal or spuriously high serum cobalamin levels, dysplastic features of ring sideroblasts in the bone marrow (BM), hemolysis, and concomitant diseases such as iron deficiency or thalassemia. Herein, the author discusses an overview of diagnostic difficulties, with regards to morphological mimics, coexisting diseases, limitations of currently available tests, and how to diagnose PA in the era of imperfect laboratory tests.

Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series.

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.

Do all the patients with gastric parietal cell antibodies have pernicious anemia?

OBJECTIVE: This study evaluated whether all the patients with serum gastric parietal cell antibody (GPCA) positivity had pernicious anemia (PA). MATERIALS AND METHODS: The blood hemoglobin (Hb), iron, and vitamin B12 concentrations, and mean corpuscular volume (MCV) in 124 GPCA-positive patients were measured and compared with the corresponding data in 124 age- and sex-matched healthy controls. PA was defined by World Health Organization (WHO) as having an Hb concentration < 13 g dl(-1) for men and < 12 g dl(-1) for women, an MCV ≥ 100 fl, and a serum vitamin B12 level < 200 pg ml(-1) . RESULTS: We found that 20, 25, and 20 GPCA-positive patients had deficiencies of Hb (men < 13 g dl(-1) , women < 12 g dl(-1) ), iron (<60 µg dl(-1) ), and vitamin B12 (<200 pg ml(-1) ), respectively. Moreover, 16 GPCA-positive patients had abnormally high MCV (≥ 100 fl). GPCA-positive patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency and of abnormally high MCV (all P-values < 0.001) than healthy controls. However, only 12.9% of 124 GPCA-positive patients were diagnosed as having PA by the WHO definition. CONCLUSION: Only 12.9% of GPCA-positive patients are discovered to have PA by the WHO definition.

[Hypergastrinaemia without detection of gastrinoma]. / Hypergastrinemie bez detekce gastrinomu.

We present a case-report of a woman with persisting gastric ulcers, who had elevated gastrin blood levels. First of all, a rare cause of hypergastrinaemia was excluded - a gastrinoma. It was not found despite of extensive investigation. Ulcers were repetitively biopted and transition of high grade dysplasia to adenocarcinoma was detected. Gastrin levels normalised after surgical antrectomia. Afterwards pernicious anaemia was diagnosed as the underlining cause of hypergastrinaemia.

Regenerating gene Iα is a biomarker for diagnosis and monitoring of celiac disease: a preliminary study.

The regenerating gene (REG) is a multigene family in humans that plays a role in tissue regeneration. The REG Iα protein is expressed in the pancreas and the gastrointestinal tract and is involved in the pathophysiology of gastritis, pancreatitis, cancer, inflammatory bowel disease, and type 1 diabetes (T1D). Celiac disease (CD) is an autoimmune disease caused by the ingestion of gluten in genetically susceptible individuals. Our aim was to determine whether the serum REG Iα concentration reflects the destructive/regenerative process in the small bowel in CD. REG Iα was determined by enzyme-linked immunosorbent assay (ELISA) in 40 patients with active CD, and in 19 of them, REG Iα was assessed after following a gluten free diet. As controls, 35 healthy subjects were included in the study. Autoantibodies to transglutaminase, gliadin, and endomisium were measured also. We found a significant increase in REG Iα in the sera of CD patients when compared with controls. REG Iα levels decreased after a gluten-free diet together with a significant reduction in antitransglutaminase antibodies. T1D and pernicious anemia patients displayed normal serum REG Iα concentrations. This preliminary study suggests that REG Iα protein levels can be used as a biomarker for the diagnosis and monitoring of CD.

Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia.

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.

Thyroid and gastric autoimmune diseases.

OBJECTIVES: Autoimmune thyroid disease (AITD) is frequently accompanied by other organ-specific diseases. We investigated the frequency of the association AITD-Biermer's disease (BD) in patients with AITD by investigating the prevalence of intrinsic factor antibodies (IF-Ab). DESIGN AND METHODS: Sera from 113 patients with AITD (hypo- or hyperthyroidism) were screened for the presence of type I IF-Ab with a competitive automated immunoassay based. Matched sera from 113 patients with dysthyroidism (not AITD) were tested. RESULTS: Four IF-Ab positive patients suffered from AITD. BD was known for two of them and strongly suspected in the two others. All patients with no AITD tested IF-Ab negative. B12 levels were often low whatever the etiology. CONCLUSION: The prevalence of IF-AbI is higher (3.5%) in patients with AITD. Prospective studies should investigate whether correcting thyroid dysfunction improves vitamin B12 levels, and establish whether routine screening for gastric autoimmunity is clinically useful or purely academic.

Folate and vitamin B12 status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK.

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.

Is there any relationship between pernicious anemia and iron deficiency?

INTRODUCTION: Previous studies have suggested that iron deficiency could be due to atrophic gastritis of the body/fundus. The aim of this study was to determine the prevalence of iron deficiency among patients with pernicious anemia and associated factors. PATIENTS AND METHODS: All patients with pernicious anemia diagnosed at our institution between January 1990 and February 2005 were included. Inclusion criteria were: 1- histological diagnosis of atrophic fundic gastritis and 2- criteria of gastric autoimmune involvement. Histology of gastric biopsies was performed in a blinded manner. Iron deficiency was defined as serum ferritin level<15 microg/L in women and<40 microg/L in men. RESULTS: Ninety-five patients (69 women), mean age 60 years (range: 23-90) were included. Twenty patients (21.1%) had normal blood cell counts; 12 patients (12.6%) had microcytosis with or without anemia and 53 patients (55.8%) macrocytosis with or without anemia. Serum ferritin levels were measured in 58 patients, 16 (27.6%) of whom, all women, had iron deficiency. They were significantly younger (39.2 years) than patients without iron deficiency (61.6 years, P<0.0001). Serum gastrin levels did not differ between the groups with and without iron deficiency. A significantly more severe inflammatory infiltrate of the fundus and endocrine cell hyperplasia was observed in iron deficiency patients. Multivariate analysis showed that iron deficiency was linked to female gender and age<50 years. CONCLUSION: Iron deficiency and microcytic anemia are not rare in patients with pernicious anemia and should not rule out the diagnosis. Iron deficiency does not appear to be related to the degree of atrophic fundic gastritis but is linked to female gender and young age, suggesting menstrual blood loss could play a role. Whether decreased iron absorption due to reduced acid secretion favors the expression of gynecological iron loss cannot be ascertained.

Coexistence of megaloblastic anemia and iron deficiency anemia in a young woman with chronic lymphocytic thyroiditis.

Pernicious anemia is a megaloblastic anemia caused by vitamin B12 deficiency, and is the end-stage of autoimmune gastritis that typically affects persons older than 60 years. It is the most common cause of vitamin B12 deficiency. Pernicious anemia can also be diagnosed concurrently with other autoimmune diseases. We report the occurrence of megaloblastic anemia in a 22-year-old woman with chronic autoimmune thyroiditis for 10.5 years. Recently, she presented with microcytic anemia, and iron deficiency anemia was diagnosed initially. After administration of ferrous sulfate, macrocytic anemia was revealed and vitamin B12 deficiency was detected. Pernicious anemia was highly suspected because of the endoscopic finding of atrophic gastritis, and high titer of antigastric parietal cell antibody, as well as elevated serum gastrin level. After intramuscular injections of hydroxycobalamine 100 microg daily for 10 days, and monthly later, her blood counts returned to normal.

New insights into the pathophysiology of cobalamin deficiency.

Cobalamin-deficient (Cbl-D) central neuropathy in the rat is associated with a locally increased expression of neurotoxic tumour necrosis factor-alpha (TNF-alpha) and a locally decreased expression of neurotrophic epidermal growth factor (EGF). These recent findings suggest that cobalamin oppositely regulates the expression of TNF-alpha and EGF, and raise the possibility that these effects might be independent of its coenzyme function. Furthermore, adult Cbl-D patients have high levels of TNF-alpha and low levels of EGF in the serum and cerebrospinal fluid. Serum levels of TNF-alpha and EGF of cobalamin-treated patients normalize concomitantly with haematological disease remission. These observations suggest that cobalamin deficiency induces an imbalance in TNF-alpha and EGF levels in biological fluids that might have a role in the pathogenesis of the damage caused by pernicious anaemia.

Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion.

Iron deficiency is a known complication of achlorhydria and may precede the development of pernicious anemia. Among 160 patients with autoimmune gastritis identified by hypergastrinemia and strongly positive antiparietal antibodies, we explored the overlap between 83 subjects presenting with iron deficiency anemia (IDA), 48 with normocytic indices, and 29 with macrocytic anemia. Compared with macrocytic patients, patients with IDA were 21 years younger (41 +/- 15 years versus 62 +/- 15 years) and mostly women. All groups had a high prevalence of thyroid disease (20%) and diabetes (8%) suggestive of the autoimmune polyendocrine syndrome. Stratification by age cohorts from younger than 20 years to older than 60 years showed a regular and progressive increase in mean corpuscular volume (MCV) from 68 +/- 9 to 95 +/- 16 fl, serum ferritin levels from 4 +/- 2 to 37 +/- 41 microg/L, gastrin level from 166 +/- 118 to 382 +/- 299 pM/L (349 +/- 247 to 800 +/- 627 pg/mL), and a decrease in cobalamin level from 392 +/- 179 to 108 +/- 65 pg/mL. The prevalence of Helicobacter pylori infection was 87.5% at age younger than 20 years, 47% at age 20 to 40 years, 37.5% at 41 to 60 years, and 12.5% at age older than 60 years. These findings challenge the common notion that pernicious anemia is a disease of the elderly and imply a disease starting many years before the establishment of clinical cobalamin deficiency, by an autoimmune process likely triggered by H pylori.

Serum pepsinogen I: an early marker of pernicious anemia in patients with type 1 diabetes.

CONTEXT: Pernicious anemia (PA) is an autoimmune organ disease much more common in type 1 diabetic patients (DM1) than in nondiabetic subjects, but it is clinically silent until its end stage. OBJECTIVE: This study aimed to determine biochemical markers of latent PA in a population of DM1 patients attending the endocrinology outpatient clinic of a university hospital. STUDY SUBJECTS: The population studied consisted of 186 unselected patients (32.4 +/- 8.7 yr) and 118 healthy controls (30.9 +/- 9.4 yr). MEASUREMENTS AND INTERVENTIONS: Plasma gastrin and pepsinogen I were determined in patients and controls, whereas hemoglobin A1c, serum cobalamin, hemoglobin, and organ-specific antibodies were determined only in patients. Latent PA was defined as serum pepsinogen I less than 30 microg/liter. In patients with low pepsinogen I concentrations and hypergastrinemia, esophagogastroduodenoscopy (EGD) was performed. RESULTS: DM1 patients showed significantly lower pepsinogen I concentrations (P < 0.001) and higher gastrinemia than controls. Latent PA was present in 12.4% of patients vs. 0.9% of controls. Among patients, more women than men showed low plasma pepsinogen I concentrations (P = 0.002) and thyroperoxidase antibody positivity (P < 0.001). Only the highest parietal cell antibody titers (> or =1:640) identified patients with significantly higher levels of plasma gastrin (P < 0.001) and lower levels of pepsinogen I (P < 0.001). The histopathological EGD findings confirmed different degrees of gastric body mucosa atrophy in all cases. CONCLUSION: The high prevalence of latent PA found in our DM1 patients leads us to recommend its screening using serum pepsinogen I concentrations. In patients with hypergastrinemia and high parietal cell antibody titers, EGD should be considered to confirm gastric mucosa atrophy.

Cases from the Osler Medical Service at Johns Hopkins University.

A 50-year-old African American woman presented with bilateral lower extremity pain, a history of falls during the past several months, and personality and behavior changes. She had been in good health until approximately 5 months before admission, when she began to fall with increasing frequency, often while going down a flight of stairs. She described these falls as her "legs giving out" and feeling very heavy and unsteady. There was no head trauma or loss of consciousness. Her daughter noticed that her gait had become somewhat unsteady during the last several months. Her family also noted a change in her personality at this time. Previously, she had been a very tidy person who took great care with her appearance, who was working as a customer service representative. However, she had become less social and very withdrawn. She had been observed putting on dirty clothes after showering, as well as eating constantly. The patient denied any fevers, chills, night sweats, headaches, vision changes, or tinnitus. She also denied any rashes, muscle pain, or intolerance to heat or cold. There was no history of seizure disorder or depression. Her past medical history was notable only for hypertension and being a passenger in a motor vehicle crash 1 year before admission. She denied any alcohol, tobacco, or illicit drug use, and had no travel history other than coming to the United States, as she was originally from Trinidad. On physical examination, she was a moderately obese African American woman with a flat affect, psychomotor slowing, and alopecia of the scalp. She was alert and oriented to person, place, and time, but had a score of 26 out of 30 on the Mini-Mental State Examination. She lost points only for recall; she had no difficulty with serial 7s. Her cranial nerves were intact and her speech was fluent, although sparse, and she did not make any paraphasic errors. Her muscle strength was 5/5 in both the upper and lower extremities. Reflexes were 2+ in the upper extremities and 1+ in the lower extremities, and toes were downgoing bilaterally. She had intact sensation to light touch and pinprick, but markedly diminished proprioception of her lower extremities bilaterally. She had a wide-based gait with a positive Romberg sign and was markedly ataxic. Rectal examination yielded a positive guaiac test with brown stool, normal tone, and no masses. The remainder of the physical examination was normal. Laboratory studies revealed pancytopenia with a hematocrit of 22.7% and a mean corpuscular volume of 118.2 fL. A peripheral smear that was performed on admission, prior to transfusion, revealed macrocytic red cells and hypersegmented neutrophils.