Skip to main content

Diagnosis and Management of Iron Deficiency in Inflammatory Bowel Disease

  • Chapter
  • First Online:
Nutritional Management of Inflammatory Bowel Diseases

Abstract

Iron deficiency and iron deficiency anemia are the most common systemic manifestation in inflammatory bowel disease (IBD) patients. Screening is recommended in all IBD patients and should be repeated every 6–12 months in patients with clinical remission and at least every 3 months in those with active disease. Although iron deficiency anemia shows usually a chronic and mostly asymptomatic course, treatment is recommended for all patients. Intravenous iron supplementation is considered first-line in the majority of patients given higher efficacy, faster response, and better tolerability. Oral formulas may even exacerbate intestinal disease activity. Supplementation for iron deficiency without anemia is more controversial and should be based on patient’s history, individual symptoms, and preferences.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell. 2010;142(1):24–38.

    Article  CAS  PubMed  Google Scholar 

  2. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2015;pii: S0140-6736(15)60865-0. doi: 10.1016/S0140-6736(15)60865-0.

    Google Scholar 

  3. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372(19):1832–43.

    Article  PubMed  Google Scholar 

  4. Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014;123(5):615–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Stevens GA, Finucane MM, De-Regil LM, et al. Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data. Lancet Glob Health. 2013;1(1):e16–25.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA. 1997;277(12):973–6.

    Article  CAS  PubMed  Google Scholar 

  7. Cogswell ME, Looker AC, Pfeiffer CM, et al. Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003–2006. Am J Clin Nutr. 2009;89(5):1334–42.

    Article  CAS  PubMed  Google Scholar 

  8. Mei Z, Cogswell ME, Looker AC, et al. Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Am J Clin Nutr. 2011;93(6):1312–20.

    Article  CAS  PubMed  Google Scholar 

  9. WHO, UNICEF, UNU. Iron deficiency anemia: assessment, prevention and control. Report of a joint WHO/UNICEF/UNU consultation. Geneva: World Health Organization; 1998.

    Google Scholar 

  10. Fourn L, Salami L. Diagnostic value of tegument pallor in anemia in pregnant women in Benin. Sante Publique. 2004;16(1):123–32.

    Article  CAS  PubMed  Google Scholar 

  11. Bager P. Fatigue and acute/chronic anaemia. Dan Med J. 2014;61(4):B4824.

    PubMed  Google Scholar 

  12. Bergsjø P, Evjen-Olsen B, Hinderaker SG, Oleking’ori N, Klepp KI. Validity of non-invasive assessment of anaemia in pregnancy. Trop Med Int Health. 2008;13(2):272–7.

    Article  PubMed  Google Scholar 

  13. Matteson KA, Raker CA, Pinto SB, Scott DM, Frishman GN. Women presenting to an emergency facility with abnormal uterine bleeding: patient characteristics and prevalence of anemia. J Reprod Med. 2012;57(1–2):17–25.

    PubMed  PubMed Central  Google Scholar 

  14. Quinn JV, Stiell IG, McDermott DA, Sellers KL, Kohn MA, Wells GA. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med. 2004;43(2):224–32.

    Article  PubMed  Google Scholar 

  15. Pizzi LT, Weston CM, Goldfarb NI, et al. Impact of chronic conditions on quality of life in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(1):47–52.

    Article  PubMed  Google Scholar 

  16. Ershler WB, Chen K, Reyes EB, Dubois R. Economic burden of patients with anemia in selected diseases. Value Health. 2005;8(6):629–38.

    Article  PubMed  Google Scholar 

  17. Wells CW, Lewis S, Barton JR, Corbett S. Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflamm Bowel Dis. 2006;12(2):123–30.

    Article  PubMed  Google Scholar 

  18. Gasche C. Anemia in IBD: the overlooked villain. Inflamm Bowel Dis. 2000;6(2):142–50; discussion 51.

    Article  CAS  PubMed  Google Scholar 

  19. Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohn’s disease. Aliment Pharmacol Ther. 2006;24(11–12):1507–23.

    Article  CAS  PubMed  Google Scholar 

  20. Gisbert JP, Gomollón F. Common misconceptions in the diagnosis and management of anemia in inflammatory bowel disease. Am J Gastroenterol. 2008;103(5):1299–307.

    Article  PubMed  Google Scholar 

  21. de la Morena F, Gisbert J. Anemia and inflammatory bowel disease. Rev Esp Enferm Dig. 2008;100(5):285–93.

    Article  PubMed  Google Scholar 

  22. Wilson A, Reyes E, Ofman J. Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature. Am J Med. 2004;116(Suppl 7A):44S–9.

    Article  PubMed  Google Scholar 

  23. Gomollón F, Gisbert JP. Anemia and inflammatory bowel diseases. World J Gastroenterol. 2009;15(37):4659–65.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010;7(11):599–610.

    CAS  PubMed  Google Scholar 

  25. Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015;9(3):211–22.

    Article  PubMed  Google Scholar 

  26. Steinbicker AU, Muckenthaler MU. Out of balance—systemic iron homeostasis in iron-related disorders. Nutrients. 2013;5(8):3034–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. McDermid JM, Lönnerdal B. Iron. Adv Nutr. 2012;3(4):532–3.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Gunshin H, Mackenzie B, Berger UV, et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature. 1997;388(6641):482–8.

    Article  CAS  PubMed  Google Scholar 

  29. McKie AT. The role of Dcytb in iron metabolism: an update. Biochem Soc Trans. 2008;36(Pt 6):1239–41.

    Article  CAS  PubMed  Google Scholar 

  30. McKie AT, Marciani P, Rolfs A, et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cell. 2000;5(2):299–309.

    Article  CAS  PubMed  Google Scholar 

  31. Donovan A, Brownlie A, Zhou Y, et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature. 2000;403(6771):776–81.

    Article  CAS  PubMed  Google Scholar 

  32. Nemeth E, Tuttle MS, Powelson J, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3.

    Article  CAS  PubMed  Google Scholar 

  33. Camaschella C. Iron and hepcidin: a story of recycling and balance. Hematology Am Soc Hematol Educ Program. 2013;2013:1–8.

    Article  PubMed  Google Scholar 

  34. Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001;96(4):1116–22.

    Article  CAS  PubMed  Google Scholar 

  35. Bernstein CN, Wajda A, Blanchard JF. The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study. Gastroenterology. 2005;129(3):827–36.

    Article  PubMed  Google Scholar 

  36. Mendoza JL, Lana R, Taxonera C, Alba C, Izquierdo S, Díaz-Rubio M. Extraintestinal manifestations in inflammatory bowel disease: differences between Crohn’s disease and ulcerative colitis. Med Clin (Barc). 2005;125(8):297–300.

    Article  Google Scholar 

  37. Ricart E, Panaccione R, Loftus EV, et al. Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2004;10(3):207–14.

    Article  PubMed  Google Scholar 

  38. Rankin GB, Watts HD, Melnyk CS, Kelley ML. National Cooperative Crohn’s Disease Study: extraintestinal manifestations and perianal complications. Gastroenterology. 1979;77(4 Pt 2):914–20.

    CAS  PubMed  Google Scholar 

  39. Su CG, Judge TA, Lichtenstein GR. Extraintestinal manifestations of inflammatory bowel disease. Gastroenterol Clin North Am. 2002;31(1):307–27.

    Article  PubMed  Google Scholar 

  40. Veloso FT, Carvalho J, Magro F. Immune-related systemic manifestations of inflammatory bowel disease. A prospective study of 792 patients. J Clin Gastroenterol. 1996;23(1):29–34.

    Article  CAS  PubMed  Google Scholar 

  41. Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106(1):110–9.

    Article  PubMed  Google Scholar 

  42. Das KM. Relationship of extraintestinal involvements in inflammatory bowel disease: new insights into autoimmune pathogenesis. Dig Dis Sci. 1999;44(1):1–13.

    Article  CAS  PubMed  Google Scholar 

  43. Monsén U, Sorstad J, Hellers G, Johansson C. Extracolonic diagnoses in ulcerative colitis: an epidemiological study. Am J Gastroenterol. 1990;85(6):711–6.

    PubMed  Google Scholar 

  44. Gasche C, Lomer MC, Cavill I, Weiss G. Iron, anaemia, and inflammatory bowel diseases. Gut. 2004;53(8):1190–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Semrin G, Fishman DS, Bousvaros A, et al. Impaired intestinal iron absorption in Crohn’s disease correlates with disease activity and markers of inflammation. Inflamm Bowel Dis. 2006;12(12):1101–6.

    Article  PubMed  PubMed Central  Google Scholar 

  46. de Silva AD, Mylonaki M, Rampton DS. Oral iron therapy in inflammatory bowel disease: usage, tolerance, and efficacy. Inflamm Bowel Dis. 2003;9(5):316–20.

    Article  PubMed  Google Scholar 

  47. Haas JD, Brownlie T. Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr. 2001;131(2S-2):676S–88; discussion 88S–90S.

    CAS  PubMed  Google Scholar 

  48. Goodnough LT, Nissenson AR. Anemia and its clinical consequences in patients with chronic diseases. Am J Med. 2004;116(Suppl 7A):1S–2.

    Article  PubMed  Google Scholar 

  49. Leitgeb C, Pecherstorfer M, Fritz E, Ludwig H. Quality of life in chronic anemia of cancer during treatment with recombinant human erythropoietin. Cancer. 1994;73(10):2535–42.

    Article  CAS  PubMed  Google Scholar 

  50. Beutler E, Waalen J. The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? Blood. 2006;107(5):1747–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Perry GS, Byers T, Yip R, Margen S. Iron nutrition does not account for the hemoglobin differences between blacks and whites. J Nutr. 1992;122(7):1417–24.

    CAS  PubMed  Google Scholar 

  52. Skikne BS, Punnonen K, Caldron PH, et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol. 2011;86(11):923–7.

    Article  CAS  PubMed  Google Scholar 

  53. Infusino I, Braga F, Dolci A, Panteghini M. Soluble transferrin receptor (sTfR) and sTfR/log ferritin index for the diagnosis of iron-deficiency anemia. A meta-analysis. Am J Clin Pathol. 2012;138(5):642–9.

    Article  PubMed  Google Scholar 

  54. Oustamanolakis P, Koutroubakis IE. Soluble transferrin receptor-ferritin index is the most efficient marker for the diagnosis of iron deficiency anemia in patients with IBD. Inflamm Bowel Dis. 2011;17(12):E158–9.

    Article  PubMed  Google Scholar 

  55. Beguin Y. Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. Clin Chim Acta. 2003;329(1–2):9–22.

    Article  CAS  PubMed  Google Scholar 

  56. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23.

    Article  CAS  PubMed  Google Scholar 

  57. Evstatiev R, Marteau P, Iqbal T, et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology. 2011;141(3):846–53. e1–2.

    Article  CAS  PubMed  Google Scholar 

  58. Lee TW, Kolber MR, Fedorak RN, van Zanten SV. Iron replacement therapy in inflammatory bowel disease patients with iron deficiency anemia: a systematic review and meta-analysis. J Crohns Colitis. 2012;6(3):267–75.

    Article  PubMed  Google Scholar 

  59. Macdougall IC, Bock AH, Carrera F, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014;29(11):2075–84.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54(2):306–15.

    CAS  PubMed  Google Scholar 

  61. Vadhan-Raj S, Strauss W, Ford D, et al. Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron. Am J Hematol. 2014;89(1):7–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Evstatiev R, Alexeeva O, Bokemeyer B, et al. Ferric carboxymaltose prevents recurrence of anemia in patients with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2013;11(3):269–77.

    Article  CAS  PubMed  Google Scholar 

  63. Kulnigg S, Stoinov S, Simanenkov V, et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol. 2008;103(5):1182–92.

    Article  CAS  PubMed  Google Scholar 

  64. de Silva AD, Tsironi E, Feakins RM, Rampton DS. Efficacy and tolerability of oral iron therapy in inflammatory bowel disease: a prospective, comparative trial. Aliment Pharmacol Ther. 2005;22(11–12):1097–105.

    Article  PubMed  Google Scholar 

  65. Seril DN, Liao J, Ho KL, Warsi A, Yang CS, Yang GY. Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice. Dig Dis Sci. 2002;47(6):1266–78.

    Article  CAS  PubMed  Google Scholar 

  66. Seril DN, Liao J, West AB, Yang GY. High-iron diet: foe or feat in ulcerative colitis and ulcerative colitis-associated carcinogenesis. J Clin Gastroenterol. 2006;40(5):391–7.

    Article  CAS  PubMed  Google Scholar 

  67. Oldenburg B, van Berge Henegouwen GP, Rennick D, Van Asbeck BS, Koningsberger JC. Iron supplementation affects the production of pro-inflammatory cytokines in IL-10 deficient mice. Eur J Clin Invest. 2000;30(6):505–10.

    Article  CAS  PubMed  Google Scholar 

  68. Rimon E, Kagansky N, Kagansky M, et al. Are we giving too much iron? Low-dose iron therapy is effective in octogenarians. Am J Med. 2005;118(10):1142–7.

    Article  CAS  PubMed  Google Scholar 

  69. Makrides M, Crowther CA, Gibson RA, Gibson RS, Skeaff CM. Efficacy and tolerability of low-dose iron supplements during pregnancy: a randomized controlled trial. Am J Clin Nutr. 2003;78(1):145–53.

    CAS  PubMed  Google Scholar 

  70. Gasche C, Ahmad T, Tulassay Z, et al. Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflamm Bowel Dis. 2015;21(3):579–88.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Santiago P. Ferrous versus ferric oral iron formulations for the treatment of iron deficiency: a clinical overview. ScientificWorldJournal. 2012;2012:846824.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Ali M, Rigolosi R, Fayemi AO, Braun EV, Frascino J, Singer R. Failure of serum ferritin levels to predict bone-marrow iron content after intravenous iron-dextran therapy. Lancet. 1982;1(8273):652–5.

    Article  CAS  PubMed  Google Scholar 

  73. Faich G, Strobos J. Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans. Am J Kidney Dis. 1999;33(3):464–70.

    Article  CAS  PubMed  Google Scholar 

  74. Okam MM, Mandell E, Hevelone N, Wentz R, Ross A, Abel GA. Comparative rates of adverse events with different formulations of intravenous iron. Am J Hematol. 2012;87(11):E123–4.

    Article  CAS  PubMed  Google Scholar 

  75. Larson DS, Coyne DW. Update on intravenous iron choices. Curr Opin Nephrol Hypertens. 2014;23(2):186–91.

    Article  CAS  PubMed  Google Scholar 

  76. Auerbach M, Ballard H, Glaspy J. Clinical update: intravenous iron for anaemia. Lancet. 2007;369(9572):1502–4.

    Article  PubMed  Google Scholar 

  77. Ganzoni AM. Intravenous iron-dextran: therapeutic and experimental possibilities. Schweiz Med Wochenschr. 1970;100(7):301–3.

    CAS  PubMed  Google Scholar 

  78. Krayenbuehl PA, Battegay E, Breymann C, Furrer J, Schulthess G. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011;118(12):3222–7.

    Article  CAS  PubMed  Google Scholar 

  79. Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361(25):2436–48.

    Article  CAS  PubMed  Google Scholar 

  80. Favrat B, Balck K, Breymann C, et al. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women—PREFER a randomized, placebo-controlled study. PLoS One. 2014;9(4):e94217.

    Article  PubMed  PubMed Central  Google Scholar 

  81. Cronin CC, Shanahan F. Anemia in patients with chronic inflammatory bowel disease. Am J Gastroenterol. 2001;96(8):2296–8.

    Article  CAS  PubMed  Google Scholar 

  82. Oldenburg B, Koningsberger JC, Van Berge Henegouwen GP, Van Asbeck BS, Marx JJ. Iron and inflammatory bowel disease. Aliment Pharmacol Ther. 2001;15(4):429–38.

    Article  CAS  PubMed  Google Scholar 

  83. Kulnigg S, Teischinger L, Dejaco C, Waldhör T, Gasche C. Rapid recurrence of IBD-associated anemia and iron deficiency after intravenous iron sucrose and erythropoietin treatment. Am J Gastroenterol. 2009;104(6):1460–7.

    Article  CAS  PubMed  Google Scholar 

  84. Nissenson AR, Wade S, Goodnough T, Knight K, Dubois RW. Economic burden of anemia in an insured population. J Manag Care Pharm. 2005;11(7):565–74.

    PubMed  Google Scholar 

  85. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  86. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in critical care investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340(6):409–17.

    Article  PubMed  Google Scholar 

  87. Bager P, Dahlerup JF. The health care cost of intravenous iron treatment in IBD patients depends on the economic evaluation perspective. J Crohns Colitis. 2010;4(4):427–30.

    Article  PubMed  Google Scholar 

  88. Hurrell R, Egli I. Iron bioavailability and dietary reference values. Am J Clin Nutr. 2010;91(5):1461S–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephan R. Vavricka M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Greuter, T., Vavricka, S.R. (2016). Diagnosis and Management of Iron Deficiency in Inflammatory Bowel Disease. In: Ananthakrishnan, A. (eds) Nutritional Management of Inflammatory Bowel Diseases. Springer, Cham. https://doi.org/10.1007/978-3-319-26890-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-26890-3_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26888-0

  • Online ISBN: 978-3-319-26890-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics