Abstract
Pernicious anemia is a macrocytic anemia due to cobalamin deficiency, which is the result of intrinsic factor deficiency. Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. Serological markers suggesting the presence of oxyntic mucosa damage are increased levels of fasting gastrin and decreased levels of Pepsinogen I. Without the now obsolete Schilling’s test, intrinsic factor deficiency may not be proven, and gastric intrinsic factor output after pentagastric stimulation has been proposed. Intrinsic factor autoantibodies are useful surrogate markers of pernicious anemia. The management of patients with pernicious anemia should focus on the life-long replacement treatment with cobalamin and the monitoring to early diagnose an eventual onset of iron deficiency. Moreover, these patients should be advised about possible gastrointestinal long-term consequences, such as gastric cancer and carcinoids.
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References
Papers of particular interest, published recently, have been highlighted as: • Of importance
Toh BH, Gleeson PA, Whittingham S, van Driel IR. Autoimmune gastritis and pernicious anemia. In: Rose NR, Mackay IR, editors. The Autoimmune diseases, 3rd edition. Academic Press; 1998. 459–76.
Bergman MP, Faller G, D’Elios MM, et al. Gastric autoimmunity. In: Mobley HLT, Mendz GL, Hazell SL, editors. Helicobacter pylori: physiology and genetics. Washington: ASM Press; 2001. Chapter 36.
De Block CEM, De Leeuw IH, Van Gaal LF. Autoimmune gastritis in type 1 diabetes. A clinically oriented review. J Clin Endocrinol Metab. 2008;93:363–71.
Lahner E, Centanni M, Agnello G, et al. Occurrence and risk factors for autoimmune thyroid disease in patients with atrophic body gastritis. Am J Med. 2008;121:136–41.
Ungar B, Mathwes JD, Tait BD, Cowling DC. HLA-DR patterns in pernicious anaemia. BMJ. 1981;282:768–70.
Amedei A, Bergman MP, Appelmelk BJ, et al. Molecular mimicry between Helicobacter pylori antigens and H+, K+ −ATPase in human gastric autoimmunity. J Exp Med. 2003;198:1147–56.
• Lahner E, Spoletini M, Buzzetti R, et al. HLA-DRB1*03 and DRB1*04 are associated with atrophic body gastritis in an Italian population. Dig Liver Dis. 2010;42:854–9. This study shows that genotypes overlapping with those reported in other autoimmune diseases are associated with autoimmune gastritis, suggesting a common immunological cluster and supporting the role of a genetic susceptibility for autoimmunity in PA.
Fernando MM, Stevens CR, Walsh EM, et al. Defining the role of the MCH in autoimmunity: a review and pooled analysis. PloS Genet. 2008;4:e1000024.
Babior BM. Erythrocyte disorders: anemias related to disturbance of DNA synthesis (megaloblastic anemias). In: Williams JW, Beutler E, Erslev AJ, Lichtman MA, editors. Hematology. 4th ed. New York: McGraw-Hill; 1998. p. 453–81.
Werder SF. Cobalamin deficiency, hyperhomocysteinemia and dementia. Neuropsychiatr Dis Treat. 2010;6:159–95.
Eisenbarth GS, Gottlieb PA. Autoimmune polyendocrine syndromes. N Engl J Med. 2004;350:2068–79.
Annibale B, Lahner E, Negrini R, et al. Lack of specific association between gastric autoimmunity hallmarks and clinical presentations of atrophic body gastritis. World J Gastroenterol. 2005;11:5351–57.
Tosetti C, Stangellini V, Tucci A, et al. Gastric emptying and dyspeptic symptoms in patients with nonautoimmune fundic atrophic gastritis. Dig Dis Sci. 2000;45:252–7.
Annibale B, Lahner E, Bordi C, et al. Role of Helicobacter pylori infection in pernicious anaemia. Dig Liver Dis. 2000;32:756–62.
Marignani M, Delle Fave G, Mecarocci S, et al. High prevalence of atrophic body gastritis in patients with unexplained microcytic and macrocytic anaemia. Am J Gastroenterol. 1999;84:766–72.
Centanni M, Gargano L, Canettieri G, et al. Thyroxine in goiter, Helicobacter pylori, and chronic gastritis. N Engl J Med. 2006;354:1787–95.
Friedlander RD. Racial factor in pernicious anaemia. Am J Med Sci. 1934;187:634.
Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med. 1996;156:1097–100.
Carmel R, Johnson CS. Racial patterns in pernicious anemia: early age at onset and increased frequency of intrinsic-factor antibody in black women. N Engl J Med. 1978;298:647–50.
Pedersen AB, Mosbeck J. Morbidity of pernicious anemia. Acta Med Scand. 1969;185:449.
Hershko C, Ronson A, Souroujon M, et al. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood. 2006;107:1673–9.
Carmel R, Weiner JM, Johnson CS. Iron deficiency occurs frequently in patients with pernicious anemia. JAMA. 1987;257:1081–3.
WHO/UNICEF/UNU. Iron deficiency anemia: assessment, prevention, and control. Geneva: World Health Organization; 2001. WHO/NHD/01.3.
Lee EL, Feldman M. Gastritis and other gastropathies. In: Feldman M, Friedman LS, Sleisenger MH, editors. Sleisenger and Fordtran’s gastrointestinal and liver disease: pathophysiology, diagnosis, management. 7th ed. Philadelphia: Saunders; 2002. p. 810–27.
Kekki M, Samloff IM, Varis K, Ihamäki T. Serum pepsinogen I and serum gastrin in the screening of severe atrophic corpus gastritis. Scand J Gastroenterol. 1991;186(suppl):109–16.
Väänänen H, Vauhkone M, Helske T, et al. Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study. Eur J Gastroenterol Hepatol. 2003;15:885–91.
Dixon MF, Genta RM, Yardley JH, Correa P. Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol. 1996;20:1161–81.
Lahner E, Annibale B. Pernicous anemia: new insights from a gastroenterological point of view. World J Gastroenterol. 2009;15:5121–8.
• Lahner E, Norman GL, Severi C, et al. Reassessment of intrinsic factor and parietal cell autoantibodies in atrophic gastritis with respect to cobalamin deficiency. Am J Gastroenterol. 2009;104:2071–9. This study highlights the diagnostic accuracy of the combined assessment of intrinsic factor and parietal cell autoantibodies for the diagnosis of pernicious anemia.
Cattan D. Pernicious anemia: what are the acutal diagnostic criteria? World J Gastroenterol. 2011;17:543–4.
Toh BH, Alderuccio F. Parietal cell and intrinsic factor autoantibodies. In: Shoenfeld Y, Gershwin ME, Meroni PL, editors. Autoantibodies. 2nd ed. Amsterdam: Elsevier; 2007. p. 479–86.
Ungar B, Whittingham S, Francis CM. Pernicious anaemia: incidence and significance of circulating antibodies to intrinsic factor and parietal cells. Aus Ann Med. 1967;16:226–9.
Davidson RJL, Atrah HI, Sewell HF. Longitudinal study of circulating antibodies in pernicious anemia. J Clin Pathol. 1989;42:1092–5.
Carmel R. Reassessment of the relative prevalence of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race. Clin Exp Immunol. 1992;89:74–7.
Annibale B, Negrini R, Caruana P, et al. Two-thirds of atrophic body gastritis patients have evidence of Helicobacter pylori infection. Helicobacter. 2001;6:225–33.
Carmel R, Perez-Perez GI, Blaser MJ. Helicobacter pylori infection and food-cobalamin malabsorption. Dig Dis Sci. 1994;39:309–14.
Cohen H, Weinstein WM, Carmel R. Heterogeneity of gastric histology and function in food cobalamin malabsorption: absence of atrophic gastritis and achlorhydria in some patients with severe malabsorption. Gut. 2000;47:638–45.
Herrmann W, Obeid R. Causes and early diagnosis of vitamin B12 deficiency. Dtsch Arztebl Int. 2008;105:680–5.
Hvas AM, Nexo E. Diagnosis and treatment of vitamin B12 deficiency—an update. Haematologica. 2006;91:1506–12.
Pruthi RK, Tefferi A. Pernicious anemia revisited. Mayo Clin Proc. 1994;69:144–50.
Bastrup-Madsed P, Helleberg-Rasmussen I, Norregaard S, et al. Long term therapy of pernicious anemia with the depot cobalamin preparation betolvex. Scand J Haematol. 1983;31:57–62.
Hathcock JN, Troendle GJ. Oral cobalamin for treatment of pernicious anemia? JAMA. 1991;265:96–7.
Lederle FA. Oral cobalamin for pernicious anemia. Medicine’s best kept secret? JAMA. 1991;265:94–5.
Andrès E, Dali-Youcef N, Vogel T, et al. Oral cobalamin (vitamin B(12)) treatment. An update. Int J Lab Hematol. 2009;31:1–8.
Correa P. Human gastric carcinogenesis: a multistep and multifactorial process. Cancer Res. 1992;52:673–5.
Wu M-S, Chen C-J, Lin J-T. Host-environment interactions: their impact on progression from gastric inflammation to carcinogenesis and on development of new approaches to prevent and treat gastric cancer. Cancer Epidemiol Biomarkers Prev. 2005;14:1878–82.
Sjoblom SM, Sipponen P, Miettinen M, et al. Gastroscopic screening for gastric carcinoids and carcinoma in pernicious anemia. Endoscopy. 1988;20:52–6.
Annibale B, Azzoni C, Corleto VD, et al. Atrophic body gastritis patients with enterochromaffin-like cell dysplasia are at increased risk for the development of type I gastric carcinoid. Eur J Gastroenterol Hepatol. 2001;13:1449–56.
Kokkola A, Sjöblom S-M, Haapiainen R, et al. The risk of gastric carcinoma and carcinoid tumours in patients with pernicious anaemia. Scand J Gastroenterol. 1998;33:88–92.
Vannella L, Sbrozzi-Vanni A, Lahner E, et al. Development of type I gastric carcinoid in patients with chronic atrophic gastritis. Aliment Pharmacol Ther. 2011. doi:10.1111/j.1365-2036.2011.04659.x [Epub ahead of print].
Uemura N, Okamoto S, Yamamoto S, et al. Helicobacter pylori and the development of gastric cancer. N Engl J Med. 2001;345:784–89.
Eisenbrand G, Adam B, Peter M, et al. Formation of nitrite in gastric juice of patients with various gastric disorders after ingestion of a standard dose of nitrate- a possible risk factor for gastric carcinogenesis. IARC Sci Publ. 1984;963:68.
Annibale B, Capurso G, Lahner E, et al. Concomitant alterations in intragastric pH and ascorbic acid concentration in patients with Helicobacter pylori gastritis and associated iron deficiency anaemia. Gut. 2003;52:496–501.
Schafer LW, Larson DE, Melton 3rd LJ, et al. Risk of development of gastric carcinoma in patients with pernicious anemia: a population-based study in Rochester, Minnesota. Mayo Clin Proc. 1985;60:444–8.
Lahner E, Bordi C, Cattaruzza MS, et al. Long-term follow-up in atrophic body gastritis patients: atrophy and intestinal metaplasia are persistent lesions irrespective of Helicobacter pylori infection. Aliment Pharmacol Ther. 2005;22:471–81.
Vannella L, Lahner E, Osborn J, et al. Risk factors for progression to gastric neoplastic lesions in patients with atrophic gastritis. Aliment Pharmacol Ther. 2010;31:1042–50.
Lahner E, Caruana P, D’Ambra G, et al. First endoscopic-histologic follow-up in patients with body-predominant atrophic gastritis: when should it be done? Gastrointest Endosc. 2001;53:443–8.
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Annibale, B., Lahner, E. & Fave, G.D. Diagnosis and Management of Pernicious Anemia. Curr Gastroenterol Rep 13, 518–524 (2011). https://doi.org/10.1007/s11894-011-0225-5
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DOI: https://doi.org/10.1007/s11894-011-0225-5