Esther Noel

Vitamin B12 (cobalamin) deficiency in elderly patients

VITAMIN B12 OR COBALAMIN DEFICIENCY occurs frequently (> 20%) among elderly people, but it is often unrecognized because the clinical manifestations are subtle; they are also potentially serious, particularly from a neuropsychiatric and hematological perspective. Causes of the deficiency include, most frequently, food-cobalamin malabsorption syndrome (> 60% of all cases), pernicious anemia (15%–20% of all cases), insufficent dietary intake and malabsorption. Food-cobalamin malabsorption, which has only recently been identified as a significant cause of cobalamin deficiency among elderly people, is characterized by the inability to release cobalamin from food or a deficiency of intestinal cobalamin transport proteins or both. We review the epidemiology and causes of cobalamin deficiency in elderly people, with an emphasis on food-cobalamin malabsorption syndrome. We also review diagnostic and management strategies for cobalamin deficiency.

Effects of oral crystalline cyanocobalamin 1000 μg/d in the treatment of pernicious anemia: An open-label, prospective study in Ten Patients.

BACKGROUND Standard treatment of cobalamin (vitamin B12) deficiency involvesregular (1000 μg/mo) IM cyanocobalamin administration. It has been suggested that high-dose (>2000 μg/d) oral cyanocobalamin may be effective in patients with pernicious anemia. OBJECTIVE The aim of this study was to assess the efficacy and tolerability of oral crystalline cyanocobalamin 1000 μg/d in patients with cobalamin deficiency related to established pernicious anemia. METHODS This open-label, prospective study was conducted at StrasbourgUniversity Hospital, Strasbourg, France. Patients aged ≥18 years with well-documented cobalamin deficiency related to pernicious anemia were enrolled. Patients received crystalline cyanocobalamin 1000 μg QD PO (capsule) for at least 3 months. Serum cobalamin, folate, iron, and homocysteine concentrations were measured, and a complete blood count was obtained, before (month 0; baseline) and after treatment. RESULTS Ten patients (7 women, 3 men; mean [SD] age, 72.1 [15.5] years) entered the study. After 3 months of treatment, serum cobalamin concentration increased in all 9 patients in whom it was measured (mean [SD] increase, 117.4 [30.8] pg/mL; P < 0.001 vs baseline). Serum cobalamin concentrations were normalized (>200 pg/mL) in 6 patients. The serum cobalamin concentration was unavailable in 1 patient because of technical problems. Eight patients had increased hemoglobin concentrations (mean [SD] increase, 2.5 [2.4] g/dL; P < 0.01 vs baseline). All 10 patients had decreased mean erythrocyte corpuscular volumes (mean [SD] decrease, 10.4 [6.2] fL; P < 0.003 vs baseline). Four patients received concomitant blood transfusions or folate and iron supplementation. Three patients experienced clinical improvement in paresthesia, reflex abolition, or combined medullary sclerosis (each, 1 patient). CONCLUSION The results of this small study in patients with cobalamin deficiencyrelated to pernicious anemia suggest that oral crystalline cyanocobalamin 1000 μg/d may be an effective treatment.

Life-Threatening Idiosyncratic Drug-Induced Agranulocytosis in Elderly Patients

Agranulocytosis is a life-threatening disorder in any age, but particularly so in elderly patients who are receiving, on average, a larger number of drugs than younger patients. Drug-induced agranulocytosis still remains a rare event, with an annual incidence rate of approximately 3–12 cases per million population. This disorder frequently occurs as an adverse reaction to drugs, particularly antibacterials, antiplatelet agents, antithyroid drugs, antipsychotics or antiepileptic drugs, and NSAIDs. Although patients experiencing drug-induced agranulocytosis may initially be asymptomatic, the severity of the neutropenia usually translates into the onset of severe sepsis that requires intravenous broad-spectrum antibacterial therapy. In this setting, haematopoietic growth factors have been shown to shorten the duration of neutropenia. Thus, with appropriate management, the mortality rate of idiosyncratic drug-induced agranulocytosis is now 5–10%. However, given the increased life expectancy and subsequent longer exposure to drugs, as well as the development of new agents, physicians should be aware of this complication and its management.

Idiopathic Thrombocytopenic Purpura A Retrospective Analysis in 139 Patients of the Influence of Age on the Response to Corticosteroids, Splenectomy and Danazol

ObjectiveTo review the influence of age on the response of patients with idiopathic thrombocytopenic purpura (ITP) to corticosteroids, splenectomy and danazol.MethodsWe retrospectively reviewed a cohort of 139 consecutively treated patients with ITP diagnosed between 1985 and 1994. In particular, we analysed the therapies used, their response rates, prognostic indicators of response and adverse effects. Furthermore, we compared the efficacy and tolerability of the various therapies between younger and older patients (<60 and ≥60 years old).ResultsCorticosteroids were used as first-line treatment in 118 patients with an initial response rate of 83%. Age did not affect the outcome of corticosteroid therapy, but all the patients aged ≥60 years reported adverse effects. A splenectomy was performed in 55 patients with an initial response rate of 87%. Older patients had significantly poorer outcomes from splenectomy with higher postoperative morbidity. Finally, danazol was given in 33 patients with a favourable response in 72% of cases. Compared with younger patients, older patients had a significantly better outcome with danazol.ConclusionsAge may have significant effects on the response to and adverse effects of therapy in ITP, and this should be considered when choosing the treatment modality for the elderly.

The value of the Von Reyn and the Duke diagnostic criteria for infective endocarditis in internal medicine practice. A study of 38 cases

BACKGROUND: The aim of our study was to compare the value of the Von Reyn and the Duke diagnostic criteria for infective endocarditis (IE) in internal medicine practice. METHODS: We determined the sensitivity and negative predictive value of these two sets of diagnostic criteria in 38 patients with established infective endocarditis who were followed in two departments of general internal medicine. The patients essentially had subacute endocarditis of the aortic valve (79%) with several systemic manifestations (100%). Microbial documentation included mainly gram-positive cocci (60%). RESULTS: With transthoracic echocardiography (TTE), the sensitivities of the Duke and the Von Reyn criteria were 65% and 35%, respectively, while with transesophageal echocardiography (TEE), these sensitivities were 75% and 35%, respectively. With TTE and TEE, the negative predictive values were 100% for the Duke diagnostic criteria versus only 71% for the Von Reyn criteria. CONCLUSIONS: This study confirms that the Duke diagnostic criteria are useful in practice for the management of patients with infective endocarditis followed in internal medicine.

Short-Term Oral Cobalamin Therapy for Food-Related Cobalamin Malabsorption

TO THE EDITOR: Oral cobalamin (vitamin B12) therapy may be effective for treating patients with cobalamin deficiency, especially those with food–cobalamin malabsorption (FCM).1 We have established that 3 months of oral cobalamin therapy is beneficial.2 To date, however, the duration of treatment has not been determined.3 We report preliminary results of an open-label, non–placebo-controlled study on 30 patients with established cobalamin deficiency (serum vitamin B12 <200 pg/mL ± homocysteine >13 μmol/L) related to FCM4 who received between 250 and 1000 μg of oral crystalline cyanocobalamin per day for at least 1 month. Methods. All patients were white (mean age 72 ± 13 y); 20 were women. Clinical findings included alteration of cognitive function (impaired concentration, memory loss, disorientation) (n = 9), sensitive peripheral neuropathy (n = 7), and ischemic stroke (n = 2). The mean pretreatment vitamin B12 and total homocysteine levels were 135 ± 32 pg/dL (range 82–192) and 20.2 ± 4.6 μmol/L (range 14–35), respectively (Table 1). All patients met the criteria for cobalamin deficiency related to FCM. No serum antibodies to intrinsic factor were detected. Schilling’s test results were normal in 10 of 10 patients who were tested (mean ± SD 57Co/58Co ratio 0.95 ± 0.1). Two patients also had mild deficiency due to low vitamin B12 intake. All the patients were treated with oral crystalline cyanocobalamin for ≥1 month. Oral cobalamin 250–1000 μg/d was administered. Compliance with therapy was good and no adverse events were reported. Results. Response to treatment is indicated in Table 1. During the first month of treatment, 87% of the patients achieved normal serum cobalamin levels; all had increased serum cobalamin levels (mean 167 pg/dL; p < 0.001 compared with baseline), evidence of medullar regeneration, and corrected initial macrocytosis. Anemia was corrected in 54%. All patients had increased hemoglobin levels (mean 0.6 g/dL), reticulocyte count (mean 35 × 103/mm3), and decreased erythrocyte cell volume (mean 3 fL) (all p < 0.05). Discussion. These findings suggest that patients with cobalamin deficiency related to FCM promptly benefit from oral crystalline cyanocobalamin. In fact, during the first month of therapy, most patients had significant improvement in serum cobalamin levels as well as in blood cell counts. These results are consistent with those observed in larger studies that used long-term (3–6 mo) or higher doses (>2000 μg/d) parenteral cyanocobalamin.2,3,5 We observed a dose–response effect of oral cyanocobalamin treatment. Limitations of our study include the small population and lack of a control group. However, because of the apparent effectiveness of oral therapy and its possible benefits compared with intramuscular treatment (e.g., better compliance, lower cost), further studies with larger sample sizes that use different cyanocobalamin doses and duration are warranted.

Paralysie faciale récidivante, syndrome de Gougerot-Sjögren primitif et carence en vitamine B12

Resume Introduction Diverses atteintes des nerfs crâniens ont ete rapportees dans le cadre du syndrome de Gougerot-Sjogren. Ainsi, des atteintes du V, du III et du VII ont ete rapportees, l’atteinte la plus caracteristique etant celle du V, surtout de sa branche inferieure. De rares paralysies faciales bien documentees ont aussi ete decrites. Observation Chez une femme de 40 ans, une PF recidivante a ete revelatrice d’un syndrome de Sjogren primitif et d’une carence en vitamine B12. Discussion La survenue de la paralysie faciale a ete rattachee au syndrome de Gougerot-Sjogren. Un role du deficit en vitamine B12 est discute.

Existe-t-il un lien entre les non-dissociations de la vitamine B12 et la maladie de biermer ?

Background A relation between food-cobalamin malabsorption and pernicious anemia has been suggested, particularly in the event of food-cobalamin malabsorption related to hypochlorhydric atrophic gastritis. Study design This work describes three cases of well-documented cobalamin deficiency related to food-cobalamin malabsorption in three women aged 56, 82 and 68 years who had atrophic gastritis (not associated with Helicobacter pylori infection) and later developed authentic pernicious anemia. Conclusions This work illustrates the potential relation between these two disorders responsible for cobalamin deficiency.

Comment: Treatment of Vitamin B12 Deficiency Anemia: Oral versus Parenteral Therapy

TO THE EDITOR: We read with great interest the review by Lane and Rojas-Fernandez (Ann Pharmacother 2002;36:1268-72) about treatment of vitamin B12 deficiency with oral versus parenteral cobalamin therapy. It is a very high-quality paper with critical review of the literature. As Lane and Rojas-Fernandez demonstrated, to date, only case reports or small studies have focused on oral vitamin B12 therapy for the treatment of cobalamin deficiencies. Thus, the ideal doses of oral cobalamin and treatment duration remain to be determined.1 They noted that, in several studies, cobalamin deficiency is not well established, be it low serum vitamin B12 concentrations or true cobalamin deficiency with biological or clinical features; nor is the etiology known, be it nutritional deficiency, pernicious anemia, or food-cobalamin malabsorption. To our knowledge, these limitations involve major difficulties with interpretation of the data. We would like to offer some elements, not reported in the review, about our experience with oral cobalamin therapy for the treatment of food-cobalamin deficiency, the leading etiology of cobalamin deficiency in adults.2 Since 1995, we have diagnosed >200 patients with established cobalamin deficiency (serum vitamin B12 concentration <200 pg/mL, confirmed in 2 samples [RIA Bayer Corp., New York]).2 More than 50 of these patients have been treated for a duration of 1 to at least 4 months with oral cobalamin ranging from 250 to 1000 μg/d. Several of these patients with established food-cobalamin deficiency have been registered in various prospective studies.3,4 In a first study, we demonstrated that 3 months of oral crystalline cyanocobalamin (mean delivery dose 650 μg/d) was effective in curing cobalamin deficiency related to food.3 All patients (n = 10) had normalization of serum vitamin B12 concentrations and significant improvements of hematologic parameters: hemoglobin increased by 1.9 g/dL (p < 0.01) as compared with baseline, and mean erythrocyte cell volume decreased by 7.8 fL (p < 0.001). Recently, we confirmed these results in 15 patients treated with oral crystalline cyanocobalamin 1000 μg/d for 1 month.4 All patients had significantly increased concentrations of serum vitamin B12 compared with baseline levels: mean increase of 187 pg/mL (p < 0.05) and improvements of hematologic parameters: hemoglobin increased by 0.4 g/dL (p < 0.01), and mean erythrocyte cell volume decreased by 1.8 fL (p < 0.05). In these 2 studies, compliance with therapy and tolerance were good (no adverse effects). Clinical features were not evaluated during therapy because some findings may be related to age or other underlying disorders. Thus, to our knowledge, oral crystalline cyanocobalamin 500–1000 μg, administered for a time span ranging from 1 to 3 months, may be useful in treating cobalamin deficiency related to food. Further studies have begun to evaluate lower doses of oral cobalamin therapy (250–500 μg/d). However, prior to clinical application, other studies (randomized) are necessary.

Respiratory Complications Lead to the Diagnosis of Chronic Granulomatous Disease in Two Adult Patients

Chronic granulomatous disease (CGD) is a primary immunodeficiency associated to multiple life-threatening bacterial and fungal infections, beginning in childhood. There are rare cases of diagnosis in adulthood. We describe here two cases of late diagnosis in adults: a 45-year-old woman and 59-year-old-man. CGD diagnosis should be considered in adult patients with unexplained infectious diseases with tissue granuloma.