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.

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.

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.

[Allergic reaction after intravenous application of vitamin B12]. / Allergische Reaktion nach i.v. Gabe von Vitamin B12.

Allergic reactions of parenteral vitamin B12 (cobalamin) for therapy of pernicious anaemia are very rare, but repeatedly described in the literature. In case of allergic reactions oral instead of intravenous substitution of vitamin B12 is tolerated. Very high dosages of vitamin B12 (1,000-2,000 microg per day) are necessary due to the underlying vitamin B12 malabsorption.

[New proposals for old vitamins]. / Nouvelles indications pour de vieilles vitamines.

Complementary to their specific metabolic actions, several vitamins are given for new previously unsuspected properties. In addition to its role in calcium absorption, vitamin D has been proven to possess beneficial effects for some autoimmune diseases, several cancers and cardiovascular illnesses. It also increases muscle strength and prevents falls particularly in elderly people. Low dose oral vitamin K supplementation is a new indication for people with unstable coumarinic anticoagulant treatment. Oral vitamin 812 administration is an alternative to the classical parenteral intramuscular administration in pernicious anemia. However, the possible antioxidant beneficial effects of vitamin A and E are largely disputed taking into account an increased mortality associated to their consumption.

Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms.

Severe vitamin B(12) deficiency produces a cluster of neurological symptoms in infants, including irritability, failure to thrive, apathy, anorexia, and developmental regression, which respond remarkably rapidly to supplementation. The underlying mechanisms may involve delayed myelination or demyelination of nerves; alteration in the S-adenosylmethionine:S-adenosylhomocysteine ratio; imbalance of neurotrophic and neurotoxic cytokines; and/or accumulation of lactate in brain cells. This review summarizes the current knowledge concerning infantile vitamin B(12) deficiency, including a pooled analysis of case studies of infants born to mothers with untreated pernicious anemia or a strict vegetarian lifestyle and a discussion of the mechanisms that may underlie the manifestations of deficiency.

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.

Oral cobalamin for pernicious anemia: back from the verge of extinction.

BACKGROUND: High dose oral cobalamin therapy was shown to be effective for pernicious anemia and other cobalamin deficiency states 30 years ago, and physicians and patients state that they would find oral therapy useful, but a survey conducted in 1989 found that physicians were generally unaware of it. OBJECTIVE: To assess physician awareness and use of oral cobalamin since 1989. DESIGN, SETTING, AND PARTICIPANTS: Minneapolis area internists not listed as having subspecialties or academic business addresses were surveyed in 1989 and in 1996. MEASUREMENTS AND RESULTS: There were 245 responses to the 1989 survey and 223 responses to the 1996 survey for response rates of 68% and 69%, respectively. The percentage of internists who ever used oral cobalamin to treat pernicious anemia increased from 0 in 1989 to 19% in 1996 (P < .001). The percentage who were aware of an effective oral cobalamin preparation for treating cobalamin deficiency states also increased significantly from 4 to 29% (P < .001). The percentage of internists who agreed with the incorrect view that sufficient quantities of cobalamin cannot be absorbed when given orally declined from 91% in 1989 to 71% in 1996 (P < .001). CONCLUSION: Minneapolis internists' awareness and use of oral cobalamin treatment for pernicious anemia increased substantially between 1989 and 1996, but the majority of internists remained unaware of this treatment option.

Does folic acid harm people with vitamin B12 deficiency?

Oral folic acid given before and during pregnancy can prevent about 75% of fetal neural tube defects. Even in large dose (20 mg daily) folic acid has never been shown to harm normal people, but it has acquired a bad reputation in pernicious anaemia. Before 1930, if untreated patients survived the anaemia, they succumbed to peripheral neuritis, subacute combined degeneration of the spinal cord, and death. The speed of this progression was extremely variable. From 1947 onwards, there were many reports of rapid neurological deterioration during administration of folic acid as sole therapy to people with pernicious anaemia. However, a review of clinical studies published before the introduction of liver and vitamin B12 therapy shows that neurological deterioration was often quite as rapid and severe in untreated patients. Oral folic acid can usually correct or prevent the anaemia of pernicious anaemia. Thus it could mask the underlying disease, and allow the development or progression of neurological deterioration, if diagnosis depended on the presence of anaemic symptoms. This possibility can readily be overcome by adequate education of doctors, so that a macrocytic anaemia is not regarded as a necessary accompanying sign of the neurological disorder. The hypothetical and avoidable side-effects of food fortification with folic acid have to be balanced against the certain benefit of preventing neural tube defects in unplanned pregnancies, and also against the probability that adults may be spared the neuropsychiatric and other ill-effects which result from inadequate dietary folic acid.

Pure red cell aplasia following pernicious anemia.

A rare case of pure red cell aplasia (PRCA) in association with pernicious anemia is reported. A 40-year-old man presented with typical clinical and laboratory features of pernicious anemia and received intramuscular injections of vitamin B12, with satisfactory response. Anemia recurred 6 months later despite continued therapy, and the patient was noted to have PRCA, which was treated successfully with two courses of high-dose bolus methylprednisolone therapy. His peripheral mononuclear cells before the therapy suppressed colony formation of early erythroid precursors (BFU-E) from normal bone marrow; such a suppressive effect was not found after recovery from anemia.

Clinical chemistry of vitamin B12.

PIP: This monograph on the clinical chemistry of vitamin B12 reviews the literature on daily requirements, methods for measurement, the effects of drugs on vitamin B12 metabolism absorption, pregnancy, clinical conditions associated with vitamin B12 deficiency, errors of metabolism, and reactions to vitamin therapy. Although only very small quantities of vitamin B12 are required to satisfy the daily requirement, a sufficient supply is stored in the liver to meet normal requirements for at least a 3-year period. A number of drugs are known to affect the absorption of vitamin B12, including neomycin, potassium chloride, p-aminosalicylic acid, and colchicine. Significantly reduced serum concentrations of vitamin B12 have been noted in users of oral contraceptives (OCs), although concentrations still remain within the limits of normal. It appears that the vitamin B12 level in OC users reestablishes itself at a different and somewhat lower level. Vitamin B12 binding protein appears to remain unchanged. A vitamin B12 deficiency is unusual in pregnant women who consume a normal, varied diet. On the other hand, lactating women whose diets are low in animal protein and dairy products may have problems providing enough vitamin B12 to meet their own and their infant's needs; supplementary oral vitamins should be considered.^ieng

Immune functions in pernicious anaemia before and during treatment with vitamin B12.

Lymphocytes and their function in patients with pernicious anaemia (PA) have been studied. E-rosette forming cells (E-RFC) and surface immunoglobulin positive (S-Ig) lymphocytes in peripheral blood, PHA responses of peripheral blood lymphocytes and tuberculin skin test (Mantoux) were studied before and during specific treatment with cyanocobalamin. First in order to test possible alterations in the metabolism of lymphocytes in PA, the effect of culture conditions was studied; the optimal conditions proved to be the same as for normal cells. The serum of PA patients as a supplement for culture medium did not differ from normal. When the patients were in remission, responses in a folate poor thymine free medium (TC 199 special) were significantly greater than those obtained using a folate rich medium (RPMI 1640) (P less than 0.01), possibly indicating activation of the salvage pathway for DNA synthesis and, therefore, increased incorporation of 125IUdR in the folate poor medium. In vitro tests did not indicate any disturbances in the functions of lymphocytes either before or during appropriate treatment as studied in 23 PA patients. However, the tuberculin skin test changed from negative to positive in 5 out of 7 cases tested.

The effect of megadose ascorbic acid ingestion on the absorption and retention of vitamin B12 in man.

Radiotracer B12 analogues, hydroxy- and cyano-cobalamin have been used to study the effects of megadose L-ascorbic acid (vitamin C) ingestion on vitamin B12 metabolism in man. By employing whole body counter techniques it has been shown that, while ascorbic acid can partially inactivate both the important dietary analogue, hydroxycobalamin, and the gastric secretion, intrinsic factor which is essential for B12 absorption, the rapid binding of the B12 analogue to intrinsic factor protects the hydroxycobalamin from attack. As a result, the absorption of hydroxcobalamin is unaffected by the simultaneous ingestion of 1 g ascorbic acid. The absorption of cyanocobalamin, the most stable analogue but not found in quantity in the diet, is slightly increased by ascorbic acid. Whole body retention studies on normal subjects ingesting 2 g ascorbic acid per day show no significant evidence of in vivo destruction of body B12 stores.

[Symptom changes and rational therapy of vitamin B12 absorption disturbances (author's transl)]. / Symptomenwandel und rationelle Therapie der Vitamin-B12-Resorptionsstörungen.

Longterm parenteral therapy with the physiological depot form of vitamin B12 (aquocobalamin) is now the treatment of choice for pernicious anemia and funicular myelopathy. An optimal dosage scheme is given. High-dose oral and intrathecal applications of viatamin B12 are also possible in the individual case. If symptoms of neurological deficiency are already present in funicular myelopathy, additional physiotherapeutic measures, supervision of bladder function, prophylaxis of decubitus ulcers and contractures are necessary.