Pernicious anemia associated with cryptogenic cirrhosis: Two case reports and a literature review.

RATIONALE: Pernicious anemia (PA) is an autoimmune gastritis that results from the destruction of gastric parietal cells and the associated lack of an intrinsic factor to bind ingested vitamin B12. While an association between PA and various liver diseases has been rarely reported, reports of associated diseases include primary biliary cholangitis, autoimmune hepatitis, and Interferon-treated hepatitis C. We present 2 cases of PA associated with cryptogenic cirrhosis (CC), which has not been previously reported in the literature. PATIENT CONCERNS: A 42-year-old man presented with fatigue, pallor, and sustained abdominal distension that had persisted for 15 days. An 87-year-old man was admitted to the hospital for an unsteady gait and loss of appetite that had persisted for 20 days. DIAGNOSES: Symptoms, laboratory tests, and imaging findings for both patients were indicative of PA and CC.Both had neurological and psychiatric symptoms during hospitalization that were ultimately linked to a vitamin B12 deficiency but not hepatic encephalopathy. INTERVENTIONS: Both patients received intramuscular injections of vitamin B12. OUTCOMES: Hemoglobin levels of the 2 patients increased gradually, and their neurological symptoms were alleviated. LESSONS: PA associated with a liver disease is rare, and the underlying mechanism can only now be clarified. We speculate that autoimmune dysfunction and chronic vitamin B12 deficiency caused by PA might be unique causes of liver cirrhosis. Additional investigations are needed to verify these findings.

An acute transfusion reaction.

We present the case of a 67-year-old man who suffered an acute anaphylactic reaction during red cell transfusion due to the presence of anti-IgA antibodies. The incidence and clinical relevance of anti-IgA antibodies in IgA deficiency is reviewed, and the wider investigation and management of acute transfusion reactions is also discussed. This case highlights the need to consider the potential risks of blood component transfusion against the purported benefit.

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.

False-normal vitamin B12 results in a patient with pernicious anaemia.

Pernicious anaemia is a common autoimmune disorder with a prevalence of approximately 4% amongst Europeans. If untreated, it can result in permanent neurological disability or death. Central to the diagnosis is establishing the presence of vitamin B12 deficiency. Concern has been raised recently regarding false-normal results obtained with competitive-binding vitamin B12 assays performed on automated biochemistry platforms in patients with pernicious anaemia due to the presence of interfering anti-intrinsic factor antibodies in the patient sample. We report a case in which diagnosis of pernicious anaemia was delayed due to false-normal vitamin B12 results. Questioning the results in light of high pre-test probability, and knowledge of the role of functional markers of vitamin B12 deficiency enabled the correct diagnosis to be made so that effective treatment could be initiated. It is crucial that those who frequently request vitamin B12 are aware of the potential problems with the available assays and how these problems can be addressed. We suggest that all patients with normal vitamin B12 levels where there is a high clinical suspicion for deficiency such as a macrocytic anaemia, neurological symptoms or megaloblastic bone marrow should have a functional assay of vitamin B12 (plasma homocysteine or methylmalonic acid) checked to further investigate for vitamin B12 deficiency.

Anemia perniciosa. Del pasado al presente / Pernicious anemia. From past to present

Actualmente, la anemia perniciosa es la causa más frecuente de déficit de vitamina B12 en los países occidentales. La lesión histológica sobre la que se sustenta es la gastritis crónica atrófica autoinmune. La destrucción de las células parietales provoca un déficit de factor intrínseco, proteína fundamental para que la vitamina B12 se absorba en el íleon terminal. Los avances que se han producido en las dos últimas décadas han reabierto el debate sobre una enfermedad que parecía olvidada por su aparente simplicidad. El nuevo papel del H. pylori, el valor de los anticuerpos anticélula parietal y antifactor intrínseco, la verdadera utilidad de los niveles séricos de vitamina B12, el riesgo de adenocarcinoma y carcinoides gástricos o el tratamiento con vitamina B12 oral, son algunos de los temas de actualidad que se analizan en profundidad en esta revisión (AU)

Pernicious anemia is currently the most common cause of vitamin B12 deficiency in Western countries. The histological lesion upon which this condition is based is autoimmune chronic atrophic gastritis. The destruction of parietal cells causes a deficiency in intrinsic factor, an essential protein for vitamin B12 absorption in the terminal ileum. Advances in the last two decades have reopened the debate on a disease that seemed to have been forgotten due to its apparent simplicity. The new role of H. pylori, the value of parietal cell antibodies and intrinsic factor antibodies, the true usefulness of serum vitamin B12 levels, the risk of adenocarcinoma and gastric carcinoids and oral vitamin B12 treatment are just some of the current issues analyzed in depth in this review (AU)

"What an Affliction": Mary Todd Lincoln's Fatal Pernicious Anemia.

To date, no single diagnosis has unified the psychiatric illness and the numerous poorly defined physical complaints that Mary Lincoln (née Todd, 1818-1882) suffered in adulthood. Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment. Long thought hypochondriacal, these findings, plus their time course and her psychopathology (irritability, delusions, hallucinations, with preserved clarity), are all consistent with vitamin B12 deficiency. Pernicious anemia most probably caused this deficiency: she lacked risk factors for other causes, and her consanguineous parents both derived from a region of Scotland having a high incidence of pernicious anemia. A diagnosis of chronic multisystem pernicious anemia would clarify the conduct of Mary Lincoln as First Lady and widow, and illuminate challenges faced by her husband, President Abraham Lincoln. Her case highlights many forgotten features of the natural history of untreated pernicious anemia and is unique in the medical literature in demonstrating such a course extending over a lifetime.

The discovery of vitamin B(12).

The discovery of vitamin B(12), the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes. The valuable contribution of clinical reports and studies of patients with pernicious anemia throughout the 19th century resulted in enough clinical definition to allow Minot and Murphy to put together the first hallmark study on treatment of the condition, leading them to a Nobel Prize. These researchers were not the first to suggest that an inadequacy of nutrients was the cause of pernicious anemia, but their particular input was a carefully designed intervention in well-characterized pernicious anemia patients, of a special diet containing large amounts of liver. They found consistent improvement in the clinical and blood status of all subjects, most of whom remained on remission indefinitely. After the successful intervention studies, the next advance was made by Castle who discovered that a gastric component, which he called intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B(12), promoting its absorption through ileal receptors. The vitamin was isolated by two groups simultaneously and was crystallized and characterized in the laboratory of Dorothy Hodgkin, contributing to her Nobel Prize in 1964. Subsequently, the various biochemical roles of vitamin B(12) were elucidated, including its important interaction with folate and their common link with megaloblastic anemia. Many of the early clinical studies recognized that vitamin B(12) deficiency also caused a severe neuropathy leading to paralysis and death, while post mortem analysis demonstrated spinal cord demyelination. Vitamin B(12) is still the subject of intense research and, in particular, its role in preventing these irreversible neurological lesions remains unclear.

Selected disorders of malabsorption.

Malabsorption syndrome encompasses numerous clinical entities that result in chronic diarrhea, abdominal distention, and failure to thrive. These disorders may be congenital or acquired and include cystic fibrosis and Shwachman-Diamond syndrome; the rare congenital lactase deficiency; glucose-galactose malabsorption; sucrase-isomaltase deficiency; adult-type hypolactasia leading to acquired lactose intolerance. The pathology may be due to impairment in absorption or digestion of nutrients resulting in Nutritional deficiency, gastrointestinal symptoms, and extra gastrointestinal symptoms. Treatment is aimed at correcting the deficiencies and symptoms to improve quality of life. Common disorders of malabsorption celiac disease, pernicious anemia, and lactase deficiency are discussed in this article.

Pernicious anemia - genetic insights.

Pernicious anemia (PA) is a complex, autoimmune, multi-factorial disease. Rapid progress has been made in the understanding of susceptibility to a spectrum of other autoimmune diseases through genome wide association studies (GWAS). However, PA has been conspicuous by its absence from this work. Here, we examine the evidence that PA has a significant heritable component through epidemiological evidence and its co-occurrence with other autoimmune diseases. Further, we consider how knowledge of the genetic susceptibility to other autoimmune diseases may provide insight into the etiology of PA.

A tissue-engineered stomach shows presence of proton pump and G-cells in a rat model, resulting in improved anemia following total gastrectomy.

Despite advances in surgical reconstruction, total gastrectomy still is accompanied by various complications, especially chronic ones, such as pernicious anemia, resulting in refractory malnutrition. As an alternative approach, we have proposed a tissue-engineered stomach as a replacement of the native stomach. This study aimed to assess the secretory functions of a tissue-engineered stomach in a rat model and the nutritional status of the recipients over an extended time period. Stomach epithelial organoid units were isolated from neonatal rats and seeded onto biodegradable polymers. These constructs were implanted into the omenta of adult recipient rats. After 3 weeks, cyst-like structures had formed, henceforth referred to as tissue-engineered stomachs. The recipient stomachs were resected and replaced by their tissue-engineered counterparts. At 24 weeks after implantation, the secretory function of the tissue-engineered stomach was evaluated using immunohistochemical staining. The hemoglobin levels and nutritional status of the recipients were compared with a control group that had undergone a simple Roux-en-Y reconstruction following total gastrectomy. Recipient rats tolerated the tissue-engineered stomachs well. X-ray examination using barium as contrast showed no bowel stenosis. Staining for proton pump alpha-subunit and gastrin demonstrated the existence of parietal cells and G-cells in the neogastric mucosa, respectively, suggesting secretory functions. The treatment group showed significantly higher hemoglobin levels than the control group, although no differences in the body weight change, total protein, or cholesterol levels were observed between the two groups. A tissue-engineered stomach has the potential to function as a food reservoir following total gastrectomy. It is conjectured that replacement with a tissue-engineered stomach might restore the proton pump parietal cells and G-cells, and thereby improve anemia after a total gastrectomy in a rat model.

Reversible nitrous oxide-induced myeloneuropathy with pernicious anemia: case report and literature review.

A previously healthy 27-year-old woman developed a subacute myeloneuropathy after receiving nitrous oxide anesthesia for dental procedures. Neurologic evaluation revealed that she was vitamin B(12) deficient due to underlying pernicious anemia. Discontinuation of nitrous oxide and supplementation with vitamin B(12) resulted in dramatic clinical improvement, with near-complete normalization of her neurologic examination. This case and published reports reviewed here emphasize that favorable outcomes are possible following prompt recognition and treatment of vitamin B(12) deficiency.

Pernicious anemia.

Pernicious anemia is severe anemia most often affecting older adults, caused by failure of the stomach to absorb vitamin B12 and characterized by abnormally large red blood cells, gastrointestinal disturbances, and lesions of the spinal cord. Pernicious anemia is caused by a lack of intrinsic factor and could be an autoimmune disorder. The identification of various autoantibodies helps in the confirmation of the diagnosis and hence towards the patient management. In such patients, oral supplements or intramuscular injections of vitamin B12 are indicated.

Helicobacter pylori link to pernicious anaemia.

An immunological classification of chronic gastritis based on the detection of Helicobacter pylori (H. pylori) antibody, parietal cell antibody, intrinsic factor antibody, is reported. H. pylori chronic gastritis, slowly progresses to atrophic gastritis, in the majority of patients; in a few patients, with genetic susceptibility to form intrinsic factor antibody, it progresses to pernicious anaemia. In majority of patients of pernicious anaemia, H. pylori gradually disappears from the gastric mucosa, on development of intestinal metaplasia in them. Atrophic gastritis results from H. pylori or non H. pylori. H. pylori infection is diagnosed in the presence of H. pylori in the gastric mucosal biopsy and/or H. pylori antibody (IgG) in the serum. The presence of the genetic factor (intrinsic factor antibody) is essential for the diagnosis of pernicious aneamia. Pernicious anaemia patients without intrinsic factor antibody, should be correctly diagnosed as atrophic gastritis, in view of the absence of the genetic factor (intrinsic factor antibody) in them.