Iron deficiency in pernicious anemia: Specific features of iron deficient patients and preliminary data on response to iron supplementation.

BACKGROUND & AIMS: While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation. METHODS: We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience. RESULTS: We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p = 0.04) and lower homocysteine levels (p = 0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p = 0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11 PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p = 0.02). CONCLUSION: The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data.

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.

[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.

Effects of vitamin B12 supplementation on pain relief in certain diseases - a literature review.

Based on current scientific reports, vitamin B12 (cobalamin), used in the treatment of pernicious anemia, may be used as a pain reliever. It has been shown to be effective in the treatment of different sorts of pain, including diabetic neuropathic, musculoskeletal, abdominal, back and spine ones, but also pain in Alzheimer's disease and pain ailments resulting from the development of neoplasms. In addition, it helps regeneration of the sensory nerves and relieves pain in eye diseases, for example in dry eye syndrome. This review summarizes recent research reports on pain-relieving properties of vitamin B12.

[Thromboembolic event and metabolic hyperhomocysteinemia: A case report and review of literature]. / Événement thromboembolique et hyperhomocystéinémie métabolique : case-report et revue de la littérature.

INTRODUCTION: Venous thromboembolic diseases have an incidence of 1.57/1000. Among patients under 50 years old, thrombophilia is assessed, the indications for which are increasingly stringent. Today, the need of plasma homocysteine assay is uncertain. OBSERVATION: Our case is a 42 year-old man, in whom a pulmonary embolism associated with macrocytosis made us discover a B12 deficiency secondary to Biermer's disease. In the literature, patients are men with an average age limit to the realisation of the assessment of thrombophilia. Not all of these patients had any causal other than hyperhomocysteinemia secondary to Biermer's disease. The support is not detailed. CONCLUSION: Hyperhomocysteinemia is probably not the only thromboembolic factor. The patient received anticoagulation and vitamin B12 supplementation. A good reading of the complete blood count is essential.

Use of hyperbaric oxygenation as an adjunctive treatment for severe pernicious anaemia in a bloodless medicine patient.

Severe anaemia in patients who cannot receive blood transfusion is an indication for the use of hyperbaric oxygen therapy (HBO). Most reports of the use of HBO for anaemia involve patients with acute blood loss. This report details a case of HBO used for a patient with severe pernicious anaemia. A 35-year-old Jehovah's Witnesses believer presented to a hospital with fatigue, dyspnoea and haemoglobin of 26 g/L. She was diagnosed with pernicious anaemia. As she could not receive blood transfusion due to her religious beliefs, vitamin B12 supplementation and HBO were administered and resulted in significant improvement in her condition. The mechanisms of action of HBO, including increased systemic plasma oxygenation, can alleviate signs and symptoms of anaemia regardless of its aetiology. HBO administration can greatly enhance the plasma arterial oxygen content, leading to clinical improvement in patients with anaemia who cannot receive blood transfusion.

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.

[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.

A Rare Cause of Pancytopenia in an Exclusively Breastfed Infant.

Vitamin B12 (B12) deficiency in infancy can present with nonspecific symptoms. We report a 5-month old exclusively breastfed full-term infant with emesis, lethargy, progressive pancytopenia, hemolysis, hypofibrinogenemia, elevated lactate dehydrogenase and a hypercellular bone marrow with dyserythropoiesis. The B12 level in the serum was undetectable. The infant's lethargy resolved within 48 hours of intramuscular B12 injection, followed by rapid improvement of pancytopenia. The asymptomatic mother had a normal hemoglobin and mean corpuscular volume, but undetectable B12 level and positive antibodies to intrinsic factor, consistent with pernicious anemia masked by folate supplementation in the mother but causing symptoms in her infant.

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.

A rare form of anemia in systemic lupus erythematosus.

Mechanisms responsible for anemia in systemic lupus erythematosus (SLE) can be immune or non-immune. A 27-year-old previously healthy woman was admitted with echymotic patches over the lower limbs for six months, multiple joint pain and fatigue for 2 months. She had severe pallor and multiple echymotic patches over the lower limbs. She was diagnosed with SLE with pernicious anemia and iron deficiency anemia. The rare association of SLE with pernicious anemia was reported previously in few patients. Treatment of SLE along with B12 supplementation is necessary for such patients. Since etiology for anemia in SLE can be of various kinds, a detailed workup for identifying the underlying mechanism is necessary.

Hypersegmented neutrophils and oval macrocytes in the setting of B12 deficiency and pancytopaenia.

Vitamin B12 deficiency is a recognised pathology in several populations, with a particular prevalence in an older adult population. We present two cases whereby vitamin B12 deficiency is the causative factor in marked pancytopaenia. Oval macrocytosis and hypersegmented neutrophils were noted on both peripheral blood samples, which are a characteristic finding in macrocytic anaemia due to B12 deficiency. Distinct underlying pathologies were identified in both cases; food-cobalamin malabsorption and pernicious anaemia. Parenteral vitamin B12 supplementation resulted in a marked reticulocytosis and rapid improvement of haematological indices in both cases. We present this series to serve as a reminder that B12 deficiency can present as life-threatening pancytopaenia.It has has multiple underlying pathologies,defined risk populations and has characteristic blood film findings which can guide investigations, diagnosis and treatment.

COEXISTENCE OF ADDISON'S DISEASE AND PERNICIOUS ANEMIA: IS THE NEW CLASSIFICATION OF AUTOIMMUNE POLYGLANDULAR SYNDROME APPROPRIATE?

A case of autoimmune polyglandular syndrome (APS) is presented. A 45-year-old man was admitted due to fatigue, malaise and inappetence. He had a history of primary hypothyroidism and was on levothyroxine substitution therapy. One year before, he was diagnosed with normocytic anemia and vitamin B12 deficiency, which was treated with vitamin B12 substitution therapy. Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. Endocrinological evaluation disclosed low morning cortisol and increased adrenocorticotropic hormone levels. Hence, the diagnosis of Addison's disease was established. Additional laboratory workup showed positive parietal cell antibodies. However, his vitamin B12 levels were increased due to vitamin B12 supplementation therapy, which was initiated earlier. Gastroscopy and histopathology of gastric mucosa confirmed atrophic gastritis. Based on prior low serum vitamin B12 levels, positive parietal cell antibodies and atrophic gastritis, the patient was diagnosed with pernicious anemia. Hydrocortisone supplementation therapy was administered and titrated according to urinary-free cortisol levels. Electrolyte disbalance and red blood cell count were normalized. This case report demonstrates rather unique features of pernicious anemia in a patient with Addison's disease. It also highlights the link between type II and type III APS. Not only do they share the same etiological factors, but also overlap in pathophysiological and clinical characteristics. This case report favors older classification of APS, which consolidates all endocrine and other organ-specific autoimmune diseases into one category. This is important since it might help avoid pitfalls in the diagnosis and treatment of patients with APS.

Advances in mechanisms, diagnosis, and treatment of pernicious anemia.

Pernicious anemia (PA) is an entity initially described in 1849 as a condition that consisted of pallor, weakness, and progressive health decline. Since then several advances led to the conclusion that PA is an autoimmune disease characterized by the deficient absorption of dietary cobalamin. It is currently recognized as the most common cause of cobalamin deficiency worldwide. We hereby review the current understanding of the disease and its neurological, hematological, and biochemical manifestations with emphasis on the diagnostic approach, treatment, and monitoring strategies. We propose an algorithm for the diagnostic approach considering the current performance and limitations of the available diagnostic tools for evaluation of cobalamin status and the presence of autoimmune chronic atrophic gastritis (CAG). Patients with PA require lifelong treatment with cobalamin replacement therapy. The current widely available treatment can be provided through enteral or parenteral cobalamin supplements, with comparable efficacy and tolerability.

Cobalamin deficiency in the elderly: aetiology and management: a study of 125 patients in a geriatric hospital.

INTRODUCTION: Cobalamin deficiency is frequent in elderly patients and the main aetiologies are food-cobalamin malabsorption and pernicious anaemia. The aim of our retrospective study was to identify the causes and methods of management of cobalamin deficiency at Nice geriatric university hospital. METHODS: A retrospective monocentric study was conducted over 14 months at Nice geriatric hospital, which included patients with cobalamin deficiency having received supplementation. The clinical and paraclinical data, etiological diagnosis, treatment and follow-up modalities were analyzed retrospectively. RESULTS: We studied 125 elderly patients whose median age was 85.5 ± 7 years. The etiological diagnosis was food-cobalamin malabsorption for 72 patients (57.6 %), nutritional cobalamin deficiency for 15 patients (12 %), pernicious anaemia for 12 patients (9.6 %) and there was no etiological diagnosis for 26 patients (20.8 %). Concerning cobalamin therapy, 111 patients (88.8 %) received oral therapy and 14 (11.2 %) intramuscular therapy. Vitamin B12 levels increased significantly after supplementation (p<0.001) but cobalamin administration varied according to the diagnoses (p<0.001) and was less effective in patients with dementia (p=0.04) and food-cobalamin malabsorption. CONCLUSION: Our study showed the importance of food-cobalamin malabsorption in etiological diagnosis in accordance with the literature, but also the non-negligible share of nutritional cobalamin deficiency. Mainly oral cobalamin supplementation was used in our study with a significant increase in vitamin B12 levels. An oral cobalamin regimen is proposed for elderly patients with cobalamin deficiency but with no severe neurological signs.

Patient journeys: diagnosis and treatment of pernicious anaemia.

BACKGROUND: Instigating a patient support group for patients with pernicious anaemia (PA) revealed dissatisfaction with its current diagnosis and treatment. The authors investigated the clinical features, patient experience of diagnosis and treatment of PA in the UK. METHODS: A total of 889 patients registered with the PA Society support group completed an online survey or postal questionnaire. Outcome measures included clinical features, length of time to diagnosis and patient satisfaction with current treatment RESULTS: One-third of patients experienced symptoms for up to 1 year before diagnosis; 14% waited more than 10 years for a diagnosis. Neurological features were highly prevalent, the most common being memory loss and poor concentration. Nearly two-thirds of respondents were dissatisfied with current treatment; 10% used a non-licensed form of B12 to supplement their prescribed injections. CONCLUSION: The diagnosis and treatment of PA should be subject to a thorough review. This article discusses the patient survey and results and makes recommendations for how the diagnosis and treatment of PA may be evaluated.

Effectiveness of the National Program of Complementary Feeding for older adults in Chile on vitamin B12 status in older adults; secondary outcome analysis from the CENEX Study (ISRCTN48153354).

BACKGROUND: Older people are at increased risk of vitamin B12 deficiency and the provision of fortified foods may be an effective way to ensure good vitamin B12 status in later life. AIM: To evaluate the effectiveness of a vitamin B12 fortified food provided by a national program of complementary food for older people on plasma vitamin B12 levels. SUBJECTS AND METHODS: A random sub-sample of 351 subjects aged 65-67 y from a large cluster randomised controlled trial provided blood samples at baseline and after 24 months of intervention. The intervention arm (10 clusters 186 participants) received a vitamin B12 fortified food designed to deliver 1.4 µg/day, while the control arm did not receive complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate levels determined by radioimmunoassay were used to estimate the effect of intervention on vitamin B12 levels, adjusting for baseline levels and sex. RESULTS: Attrition at 24 months was 16.7% and 23.6% in the intervention and control arms respectively (p = 0.07). Over 24 months of intervention, mean (95% CI) serum vitamin B12 decreased from 392 (359-425) pmol/dL to 357 (300-414) pmol/dL (p < 0.07) in the intervention arm and from 395 (350-440) pmol/dL to 351 (308-395) pmol/dL in the control arm. There was no significant effect of the intervention on folate status. DISCUSSION: Our findings suggest that foods fortified with 1.4 µg/daily vitamin B12 as provided by Chile's national programme for older people are insufficient to ensure adequate vitamin B12 levels in this population. Chile has a long and successful experience with nutrition intervention programs; however, the country's changing demographic and nutritional profiles require a constant adjustment of the programs.