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Clinical Reviews in Allergy & Immunology

, Volume 55, Issue 3, pp 368–378 | Cite as

Unmet Needs in IBD: the Case of Fatigue

  • Pieter Hindryckx
  • Debby Laukens
  • Ferdinando D’Amico
  • Silvio Danese
Article
  • 526 Downloads

Abstract

Fatigue is a highly prevalent but relatively ignored problem in IBD patients. It is one of the most burdensome symptoms to the patient with an important impact on the quality of life. Therefore, fatigue is a highly relevant patient-reported outcome that should be included not only in disease activity measurement but also in the endpoints of clinical trials in IBD. However, most of the currently available scoring systems to quantify fatigue are not specifically designed for patients with IBD and none of them has undergone a complete validation process for IBD-related fatigue. Fatigue is more prevalent in patients with active disease and may improve or disappear when remission is reached. Far more complex is the persistence or onset of fatigue in quiescent IBD which presents in up to 40% of the patients. In this subgroup of patients, fatigue can be related to smoldering systemic inflammation, a poor sleep quality, anemia, nutritional deficiencies, or comorbidities. In most cases, however, no direct cause can be identified. The lack of knowledge on the mechanisms that drive fatigue in IBD hamper the development of specific drugs to treat the condition and only psychological support can be offered to the patient. Rodent models are indispensable to increase our understanding of the molecular pathways that lead to fatigue in chronic intestinal inflammation, and to develop novel therapies.

Keywords

Fatigue Inflammatory bowel disease Crohn’s disease Ulcerative colitis 

Abbreviations

CD

Crohn’s disease

CIS

Checklist Individual Strength

EQ-5D

EuroQol-5D

FACIT-F

Functional Assessment of Chronic Illness Therapy-Fatigue

HADS

Hospital Anxiety and Depression Scale

IBD

Inflammatory bowel disease

IBD-F

Inflammatory bowel disease fatigue

IBDQ

Inflammatory Bowel Disease Questionnaire

MAF

Multidimensional Assessment of Fatigue

MFI

Multidimensional Fatigue Inventory

RCT

Randomized clinical trial

TNF

Tumor necrosis factor

QoL

Quality of life

UC

Ulcerative colitis

VAS

Visual Analog Scale

Notes

Compliance with Ethical Standards

Conflict of Interest

Pieter Hindryckx has received consulting fees from Abbvie, Takeda, and Janssen; and speaker’s fees from Ferring, Falk Pharma, Vifor Pharma, Tillotts Pharma, Chiesi, Takeda, and Abbvie.

Debby Laukens reports no conflicts of interest.

Ferdinando D’Amico reports no conflicts of interest.

Silvio Danese has served as a speaker, a consultant, and an advisory board member for Abbvie, Allergan, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Ferring, Hospira, Johnson & Johnson, Merck, MSD, Takeda, Mundipharma, Pfizer, Sandoz, Tigenix, UCB Pharma, and Vifor.

References

  1. 1.
    Ordas I, Eckmann L, Talamini M, Baumgart DC, Sandborn WJ (2012) Ulcerative colitis. Lancet (Lond, Engl) 380(9853):1606–1619.  https://doi.org/10.1016/s0140-6736(12)60150-0 CrossRefGoogle Scholar
  2. 2.
    Baumgart DC, Sandborn WJ (2012) Crohn’s disease. Lancet (Lond, Engl) 380(9853):1590–1605.  https://doi.org/10.1016/s0140-6736(12)60026-9 CrossRefGoogle Scholar
  3. 3.
    Williet N, Sarter H, Gower-Rousseau C, Adrianjafy C, Olympie A, Buisson A et al (2017) Patient-reported outcomes in a French nationwide survey of inflammatory bowel disease patients. J Crohns Colitis 11(2):165–174.  https://doi.org/10.1093/ecco-jcc/jjw145 CrossRefPubMedGoogle Scholar
  4. 4.
    Farrell D, McCarthy G, Savage E (2016) Self-reported symptom burden in individuals with inflammatory bowel disease. J Crohns Colitis. 10(3):315–322.  https://doi.org/10.1093/ecco-jcc/jjv218 CrossRefPubMedGoogle Scholar
  5. 5.
    Hashash JG, Ramos-Rivers C, Youk A, Chiu WK, Duff K, Regueiro M et al (2016) Quality of sleep and coexistent psychopathology have significant impact on fatigue burden in patients with inflammatory bowel disease. J Clin Gastroenterol.  https://doi.org/10.1097/mcg.0000000000000729 CrossRefGoogle Scholar
  6. 6.
    van Langenberg DR, Gibson PR (2010) Systematic review: fatigue in inflammatory bowel disease. Aliment Pharmacol Ther 32(2):131–143.  https://doi.org/10.1111/j.1365-2036.2010.04347.x CrossRefPubMedGoogle Scholar
  7. 7.
    Grimstad T, Norheim KB, Isaksen K, Leitao K, Hetta AK, Carlsen A et al (2015) Fatigue in newly diagnosed inflammatory bowel disease. J Crohns Colitis 9(9):725–730.  https://doi.org/10.1093/ecco-jcc/jjv091 CrossRefPubMedGoogle Scholar
  8. 8.
    Opheim R, Fagermoen MS, Bernklev T, Jelsness-Jorgensen LP, Moum B (2014) Fatigue interference with daily living among patients with inflammatory bowel disease. Qual Life Res Int J Qual Life Asp Treat Care Rehab 23(2):707–717.  https://doi.org/10.1007/s11136-013-0508-4 CrossRefGoogle Scholar
  9. 9.
    Romkens TE, van Vugt-van Pinxteren MW, Nagengast FM, van Oijen MG, de Jong DJ (2011) High prevalence of fatigue in inflammatory bowel disease: a case control study. J Crohns Colitis. 5(4):332–337.  https://doi.org/10.1016/j.crohns.2011.02.008 CrossRefPubMedGoogle Scholar
  10. 10.
    DeFilippis EM, Tabani S, Warren RU, Christos PJ, Bosworth BP, Scherl EJ (2016) Exercise and self-reported limitations in patients with inflammatory bowel disease. Dig Dis Sci 61(1):215–220.  https://doi.org/10.1007/s10620-015-3832-4 CrossRefPubMedGoogle Scholar
  11. 11.
    IsHak WW, Pan D, Steiner AJ, Feldman E, Mann A, Mirocha J et al (2017) Patient-reported outcomes of quality of life, functioning, and GI/psychiatric symptom severity in patients with inflammatory bowel disease (IBD). Inflamm Bowel Dis 23(5):798–803.  https://doi.org/10.1097/mib.0000000000001060 CrossRefPubMedGoogle Scholar
  12. 12.
    Holko P, Kawalec P, Mossakowska M, Pilc A (2016) Health-related quality of life impairment and indirect cost of Crohn’s disease: a self-report study in Poland. PLoS One 11(12):e0168586.  https://doi.org/10.1371/journal.pone.0168586 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Zand A, van Deen WK, Inserra EK, Hall L, Kane E, Centeno A et al (2015) Presenteeism in inflammatory bowel diseases: a hidden problem with significant economic impact. Inflamm Bowel Dis 21(7):1623–1630.  https://doi.org/10.1097/mib.0000000000000399 CrossRefPubMedGoogle Scholar
  14. 14.
    Dibley L, Bager P, Czuber-Dochan W, Farrell D, Jelsness-Jorgensen LP, Kemp K et al (2017) Identification of research priorities for inflammatory bowel disease nursing in Europe: a Nurses-European Crohn’s and Colitis Organisation Delphi Survey. J Crohns Colitis. 11(3):353–359.  https://doi.org/10.1093/ecco-jcc/jjw164 CrossRefPubMedGoogle Scholar
  15. 15.
    Hart AL, Lomer M, Verjee A, Kemp K, Faiz O, Daly A et al (2017) What are the top 10 research questions in the treatment of inflammatory bowel disease? A priority setting partnership with the James Lind Alliance. J Crohns Colitis. 11(2):204–211.  https://doi.org/10.1093/ecco-jcc/jjw144 CrossRefPubMedGoogle Scholar
  16. 16.
    Peyrin-Biroulet L, Panes J, Sandborn WJ, Vermeire S, Danese S, Feagan BG et al (2016) Defining disease severity in inflammatory bowel diseases: current and future directions. Clin Gastroenterol Hepatol 14(3):348–54.e17.  https://doi.org/10.1016/j.cgh.2015.06.001 CrossRefPubMedGoogle Scholar
  17. 17.
    Barsevick AM, Cleeland CS, Manning DC, O'Mara AM, Reeve BB, Scott JA et al (2010) ASCPRO recommendations for the assessment of fatigue as an outcome in clinical trials. J Pain Symptom Manag 39(6):1086–1099.  https://doi.org/10.1016/j.jpainsymman.2010.02.006 CrossRefGoogle Scholar
  18. 18.
    Hjollund NH, Andersen JH, Bech P (2007) Assessment of fatigue in chronic disease: a bibliographic study of fatigue measurement scales. Health Qual Life Outcomes 5:12.  https://doi.org/10.1186/1477-7525-5-12 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dittner AJ, Wessely SC, Brown RG (2004) The assessment of fatigue: a practical guide for clinicians and researchers. J Psychosom Res 56(2):157–170.  https://doi.org/10.1016/S0022-3999(03)00371-4 CrossRefPubMedGoogle Scholar
  20. 20.
    Czuber-Dochan W, Ream E, Norton C (2013) Review article: description and management of fatigue in inflammatory bowel disease. Aliment Pharmacol Ther 37(5):505–516.  https://doi.org/10.1111/apt.12205 CrossRefPubMedGoogle Scholar
  21. 21.
    Vogelaar L, van't Spijker A, van Tilburg AJ, Kuipers EJ, Timman R, van der Woude CJ (2013) Determinants of fatigue in Crohn’s disease patients. Eur J Gastroenterol Hepatol 25(2):246–251.  https://doi.org/10.1097/MEG.0b013e32835aba83 CrossRefPubMedGoogle Scholar
  22. 22.
    Vogelaar L, van't Spijker A, Timman R, van Tilburg AJP, Bac D, Vogelaar T et al (2014) Fatigue management in patients with IBD: a randomised controlled trial. Gut 63(6):911–918.  https://doi.org/10.1136/gutjnl-2013-305191 CrossRefPubMedGoogle Scholar
  23. 23.
    Norton C, Czuber-Dochan W, Bassett P, Berliner S, Bredin F, Darvell M et al (2015) Assessing fatigue in inflammatory bowel disease: comparison of three fatigue scales. Aliment Pharmacol Ther 42(2):203–211.  https://doi.org/10.1111/apt.13255 CrossRefPubMedGoogle Scholar
  24. 24.
    Brandse JF, Vos LM, Jansen J, Schakel T, Ponsioen CI, van den Brink GR et al (2015) Serum concentration of anti-TNF antibodies, adverse effects and quality of life in patients with inflammatory bowel disease in remission on maintenance treatment. J Crohns Colitis 9(11):973–981.  https://doi.org/10.1093/ecco-jcc/jjv116 CrossRefPubMedGoogle Scholar
  25. 25.
    Grimstad T, Norheim KB, Kvaloy JT, Isaksen K, Leitao K, Carlsen A et al (2016) Conventional treatment regimens for ulcerative colitis alleviate fatigue—an observational cohort study. Scand J Gastroenterol 51(10):1213–1219.  https://doi.org/10.1080/00365521.2016.1195869 CrossRefPubMedGoogle Scholar
  26. 26.
    Artom M, Czuber-Dochan W, Sturt J, Murrells T, Norton C (2017) The contribution of clinical and psychosocial factors to fatigue in 182 patients with inflammatory bowel disease: a cross-sectional study. Aliment Pharmacol Ther 45(3):403–416.  https://doi.org/10.1111/apt.13870 CrossRefPubMedGoogle Scholar
  27. 27.
    Vogelaar L, de Haar C, Aerts BR, Peppelenbosch MP, Timman R, Hanssen BE et al (2017) Fatigue in patients with inflammatory bowel disease is associated with distinct differences in immune parameters. Clin Exp Gastroenterol 10:83–90.  https://doi.org/10.2147/ceg.s123942 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Artom M, Czuber-Dochan W, Sturt J, Norton C (2017) Cognitive behavioural therapy for the management of inflammatory bowel disease-fatigue with a nested qualitative element: study protocol for a randomised controlled trial. Trials 18(1):213.  https://doi.org/10.1186/s13063-017-1926-3 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Huppertz-Hauss G, Hoivik ML, Jelsness-Jorgensen LP, Opheim R, Henriksen M, Hoie O et al (2017) Fatigue in a population-based cohort of patients with inflammatory bowel disease 20 years after diagnosis: the IBSEN study. Scand J Gastroenterol 52(3):351–358.  https://doi.org/10.1080/00365521.2016.1256425 CrossRefPubMedGoogle Scholar
  30. 30.
    Tew GA, Carpenter R, Seed M, Anderson S, Langmead L, Fairhurst C et al (2017) Feasibility of high-intensity interval training and moderate-intensity continuous training in adults with inactive or mildly active Crohn’s disease: study protocol for a randomised controlled trial. Pilot Feasibility Stud 3:17.  https://doi.org/10.1186/s40814-017-0133-z CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Smets EM, Garssen B, Bonke B, De Haes JC (1995) The Multidimensional Fatigue Inventory (MFI) psychometric qualities of an instrument to assess fatigue. J Psychosom Res 39(3):315–325CrossRefGoogle Scholar
  32. 32.
    Belza BL, Henke CJ, Yelin EH, Epstein WV, Gilliss CL (1993) Correlates of fatigue in older adults with rheumatoid arthritis. Nurs Res 42(2):93–99CrossRefGoogle Scholar
  33. 33.
    Vercoulen J, Albert M, Bleijenberg G (1999) De Checklist Individual Strength (CIS). Gedragstherapie 32:131–136Google Scholar
  34. 34.
    Alberts M, Smets EM, Vercoulen JH, Garssen B, Bleijenberg G (1997) ‘Abbreviated fatigue questionnaire’: a practical tool in the classification of fatigue. Ned Tijdschr Geneeskd 141(31):1526–1530PubMedGoogle Scholar
  35. 35.
    Czuber-Dochan W, Norton C, Bassett P, Berliner S, Bredin F, Darvell M et al (2014) Development and psychometric testing of inflammatory bowel disease fatigue (IBD-F) patient self-assessment scale. J Crohns Colitis. 8(11):1398–1406.  https://doi.org/10.1016/j.crohns.2014.04.013 CrossRefPubMedGoogle Scholar
  36. 36.
    Wolfe F (2004) Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. J Rheumatol 31(10):1896–1902PubMedGoogle Scholar
  37. 37.
    Irvine EJ, Feagan B, Rochon J, Archambault A, Fedorak RN, Groll A et al (1994) Quality of life: a valid and reliable measure of therapeutic efficacy in the treatment of inflammatory bowel disease. Canadian Crohn’s Relapse Prevention Trial Study Group. Gastroenterology 106(2):287–296CrossRefGoogle Scholar
  38. 38.
    Cheung WY, Garratt AM, Russell IT, Williams JG (2000) The UK IBDQ-a British version of the inflammatory bowel disease questionnaire. Development and validation. J Clin Epidemiol 53(3):297–306CrossRefGoogle Scholar
  39. 39.
    Johnson JA, Coons SJ, Ergo A, Szava-Kovats G (1998) Valuation of EuroQOL (EQ-5D) health states in an adult US sample. PharmacoEconomics 13(4):421–433CrossRefGoogle Scholar
  40. 40.
    Snaith RP, Zigmond AS (1986) The hospital anxiety and depression scale. Br Med J (Clin Res Ed) 292(6516):344CrossRefGoogle Scholar
  41. 41.
    Lovibond PF, Lovibond SH (1995) The structure of negative emotional states: comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories. Behav Res Ther 33(3):335–343CrossRefGoogle Scholar
  42. 42.
    Bager P, Befrits R, Wikman O, Lindgren S, Moum B, Hjortswang H et al (2012) Fatigue in out-patients with inflammatory bowel disease is common and multifactorial. Aliment Pharmacol Ther 35(1):133–141.  https://doi.org/10.1111/j.1365-2036.2011.04914.x CrossRefPubMedGoogle Scholar
  43. 43.
    Kappelman MD, Long MD, Martin C, DeWalt DA, Kinneer PM, Chen W et al (2014) Evaluation of the patient-reported outcomes measurement information system in a large cohort of patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 12(8):1315–23.e2.  https://doi.org/10.1016/j.cgh.2013.10.019 CrossRefPubMedGoogle Scholar
  44. 44.
    Graff LA, Clara I, Walker JR, Lix L, Carr R, Miller N et al (2013) Changes in fatigue over 2 years are associated with activity of inflammatory bowel disease and psychological factors. Clin Gastroenterol Hepatol 11(9):1140–1146.  https://doi.org/10.1016/j.cgh.2013.03.031 CrossRefPubMedGoogle Scholar
  45. 45.
    Yoo S, Jung YS, Park JH, Kim HJ, Cho YK, Sohn CI et al (2014) Fatigue severity and factors associated with high fatigue levels in Korean patients with inflammatory bowel disease. Gut Liver 8(2):148–153.  https://doi.org/10.5009/gnl.2014.8.2.148 CrossRefPubMedGoogle Scholar
  46. 46.
    Dantzer R (2009) Cytokine, sickness behavior, and depression. Immunol Allergy Clin N Am 29(2):247–264.  https://doi.org/10.1016/j.iac.2009.02.002 CrossRefGoogle Scholar
  47. 47.
    Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 9(1):46–56.  https://doi.org/10.1038/nrn2297 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Abautret-Daly A, Dempsey E, Parra-Blanco A, Medina C, Harkin A (2017) Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease. Acta Neuropsychiatr:1–22.  https://doi.org/10.1017/neu.2017.3 CrossRefGoogle Scholar
  49. 49.
    Louati K, Berenbaum F (2015) Fatigue in chronic inflammation—a link to pain pathways. Arthritis Res Ther 17:254.  https://doi.org/10.1186/s13075-015-0784-1 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Jelsness-Jorgensen LP, Bernklev T, Henriksen M, Torp R, Moum BA (2011) Chronic fatigue is more prevalent in patients with inflammatory bowel disease than in healthy controls. Inflamm Bowel Dis 17(7):1564–1572.  https://doi.org/10.1002/ibd.21530 CrossRefPubMedGoogle Scholar
  51. 51.
    Goldenberg BA, Graff LA, Clara I, Zarychanski R, Walker JR, Carr R et al (2013) Is iron deficiency in the absence of anemia associated with fatigue in inflammatory bowel disease? Am J Gastroenterol 108(9):1392–1397.  https://doi.org/10.1038/ajg.2013.14 CrossRefPubMedGoogle Scholar
  52. 52.
    Cekic C, Ipek S, Aslan F, Akpinar Z, Arabul M, Topal F et al (2015) The effect of intravenous iron treatment on quality of life in inflammatory bowel disease patients with nonanemic iron deficiency. Gastroenterol Res Pract 2015:582163.  https://doi.org/10.1155/2015/582163 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Eliadou E, Kini G, Huang J, Champion A, Inns SJ (2017) Intravenous iron replacement improves quality of life in hypoferritinemic inflammatory bowel disease patients with and without anemia. Dig Dis (Basel, Switz).  https://doi.org/10.1159/000468145 CrossRefGoogle Scholar
  54. 54.
    Maes M, Mihaylova I, De Ruyter M (2006) Lower serum zinc in chronic fatigue syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affect Disord 90(2–3):141–147.  https://doi.org/10.1016/j.jad.2005.11.002 CrossRefPubMedGoogle Scholar
  55. 55.
    Jacobson W, Saich T, Borysiewicz LK, Behan WM, Behan PO, Wreghitt TG (1993) Serum folate and chronic fatigue syndrome. Neurology 43(12):2645–2647CrossRefGoogle Scholar
  56. 56.
    Huijts M, Duits A, Staals J, van Oostenbrugge RJ (2012) Association of vitamin B12 deficiency with fatigue and depression after lacunar stroke. PLoS One 7(1):e30519.  https://doi.org/10.1371/journal.pone.0030519 CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Han B, Wu X, Guo Y (2017) Improvement of fatigue after vitamin D supplementation in kidney transplant recipients. Medicine 96(21):e6918.  https://doi.org/10.1097/md.0000000000006918 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Minderhoud IM, Oldenburg B, van Dam PS, van Berge Henegouwen GP (2003) High prevalence of fatigue in quiescent inflammatory bowel disease is not related to adrenocortical insufficiency. Am J Gastroenterol 98(5):1088–1093.  https://doi.org/10.1111/j.1572-0241.2003.07414.x CrossRefPubMedGoogle Scholar
  59. 59.
    Shizuma T (2016) Concomitant thyroid disorders and inflammatory bowel disease: a literature review. Biomed Res Int 2016:5187061.  https://doi.org/10.1155/2016/5187061 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Minderhoud IM, Samsom M, Oldenburg B (2007) Crohn’s disease, fatigue, and infliximab: is there a role for cytokines in the pathogenesis of fatigue? World J Gastroenterol 13(14):2089–2093CrossRefGoogle Scholar
  61. 61.
    Loftus EV, Feagan BG, Colombel JF, Rubin DT, Wu EQ, Yu AP et al (2008) Effects of adalimumab maintenance therapy on health-related quality of life of patients with Crohn’s disease: patient-reported outcomes of the CHARM trial. Am J Gastroenterol 103(12):3132–3141.  https://doi.org/10.1111/j.1572-0241.2008.02175.x CrossRefPubMedGoogle Scholar
  62. 62.
    Jelsness-Jorgensen LP, Bernklev T, Henriksen M, Torp R, Moum BA (2011) Chronic fatigue is associated with impaired health-related quality of life in inflammatory bowel disease. Aliment Pharmacol Ther 33(1):106–114.  https://doi.org/10.1111/j.1365-2036.2010.04498.x CrossRefPubMedGoogle Scholar
  63. 63.
    Lee TW, Iser JH, Sparrow MP, Newnham ED, Headon BJ, Gibson PR (2009) Thiopurines, a previously unrecognised cause for fatigue in patients with inflammatory bowel disease. J Crohns Colitis. 3(3):196–199.  https://doi.org/10.1016/j.crohns.2009.03.004 CrossRefPubMedGoogle Scholar
  64. 64.
    van Langenberg DR, Gibson PR (2014) Factors associated with physical and cognitive fatigue in patients with Crohn’s disease: a cross-sectional and longitudinal study. Inflamm Bowel Dis 20(1):115–125.  https://doi.org/10.1097/01.mib.0000437614.91258.70 CrossRefPubMedGoogle Scholar
  65. 65.
    Graff LA, Vincent N, Walker JR, Clara I, Carr R, Ediger J et al (2011) A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflamm Bowel Dis 17(9):1882–1889.  https://doi.org/10.1002/ibd.21580 CrossRefPubMedGoogle Scholar
  66. 66.
    Opheim R, Fagermoen MS, Jelsness-Jorgensen LP, Bernklev T, Moum B (2014) Sense of coherence in patients with inflammatory bowel disease. Gastroenterol Res Pract 2014:989038.  https://doi.org/10.1155/2014/989038 CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Banovic I, Gilibert D, Jebrane A, Cosnes J (2012) Personality and fatigue perception in a sample of IBD outpatients in remission: a preliminary study. J Crohns Colitis. 6(5):571–577.  https://doi.org/10.1016/j.crohns.2011.11.006 CrossRefPubMedGoogle Scholar
  68. 68.
    Harrington ME (2012) Neurobiological studies of fatigue. Prog Neurobiol 99(2):93–105.  https://doi.org/10.1016/j.pneurobio.2012.07.004 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Sorge RE, Martin LJ, Isbester KA, Sotocinal SG, Rosen S, Tuttle AH et al (2014) Olfactory exposure to males, including men, causes stress and related analgesia in rodents. Nat Methods 11(6):629–632.  https://doi.org/10.1038/nmeth.2935 CrossRefPubMedGoogle Scholar
  70. 70.
    Ray MA, Trammell RA, Verhulst S, Ran S, Toth LA (2011) Development of a mouse model for assessing fatigue during chemotherapy. Comp Med 61(2):119–130PubMedPubMedCentralGoogle Scholar
  71. 71.
    Zombeck JA, Fey EG, Lyng GD, Sonis ST (2013) A clinically translatable mouse model for chemotherapy-related fatigue. Comp Med. 63(6):491–497PubMedPubMedCentralGoogle Scholar
  72. 72.
    Can A, Dao DT, Arad M, Terrillion CE, Piantadosi SC, Gould TD (2012) The mouse forced swim test. J Vis Exp 59:e3638.  https://doi.org/10.3791/3638 CrossRefGoogle Scholar
  73. 73.
    Page ME, Detke MJ, Dalvi A, Kirby LG, Lucki I (1999) Serotonergic mediation of the effects of fluoxetine, but not desipramine, in the rat forced swimming test. Psychopharmacology 147(2):162–167CrossRefGoogle Scholar
  74. 74.
    Kulesskaya N, Voikar V (2014) Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure. Physiol Behav 133:30–38.  https://doi.org/10.1016/j.physbeh.2014.05.006 CrossRefPubMedGoogle Scholar
  75. 75.
    Strober W (2008) Why study animal models of IBD? Inflamm Bowel Dis 14(Suppl 2):S129–S131.  https://doi.org/10.1002/ibd.20667 CrossRefPubMedGoogle Scholar
  76. 76.
    Cramp F, Hewlett S, Almeida C, Kirwan JR, Choy EH, Chalder T, Pollock J, Christensen R (2013) Non-pharmacological interventions for fatigue in rheumatoid arthritis. Cochrane Database Syst Rev (8):CD008322.  https://doi.org/10.1002/14651858.CD008322.pub2
  77. 77.
    Loudon CP, Corroll V, Butcher J, Rawsthorne P, Bernstein CN (1999) The effects of physical exercise on patients with Crohn’s disease. Am J Gastroenterol 94(3):697–703.  https://doi.org/10.1111/j.1572-0241.1999.00939.x CrossRefPubMedGoogle Scholar
  78. 78.
    Vogelaar L, van den Berg-Emons R, Bussmann H, Rozenberg R, Timman R, van der Woude CJ (2015) Physical fitness and physical activity in fatigued and non-fatigued inflammatory bowel disease patients. Scand J Gastroenterol 50(11):1357–1367.  https://doi.org/10.3109/00365521.2015.1046135 CrossRefPubMedGoogle Scholar
  79. 79.
    Nathan I, Norton C, Czuber-Dochan W, Forbes A (2013) Exercise in individuals with inflammatory bowel disease. Gastroenterol Nurs 36(6):437–442.  https://doi.org/10.1097/sga.0000000000000005 CrossRefPubMedGoogle Scholar
  80. 80.
    Tew GA, Jones K, Mikocka-Walus A (2016) Physical activity habits, limitations, and predictors in people with inflammatory bowel disease: a large cross-sectional online survey. Inflamm Bowel Dis 22(12):2933–2942.  https://doi.org/10.1097/mib.0000000000000962 CrossRefPubMedGoogle Scholar
  81. 81.
    McCombie AM, Mulder RT, Gearry RB (2013) Psychotherapy for inflammatory bowel disease: a review and update. J Crohns Colitis. 7(12):935–949.  https://doi.org/10.1016/j.crohns.2013.02.004 CrossRefPubMedGoogle Scholar
  82. 82.
    Vogelaar L, van't Spijker A, Timman R, van Tilburg AJ, Bac D, Vogelaar T et al (2014) Fatigue management in patients with IBD: a randomised controlled trial. Gut 63(6):911–918.  https://doi.org/10.1136/gutjnl-2013-305191 CrossRefPubMedGoogle Scholar
  83. 83.
    Garcia-Vega E, Fernandez-Rodriguez C (2004) A stress management programme for Crohn’s disease. Behav Res Ther 42(4):367–383.  https://doi.org/10.1016/s0005-7967(03)00146-3 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Pieter Hindryckx
    • 1
  • Debby Laukens
    • 1
  • Ferdinando D’Amico
    • 2
  • Silvio Danese
    • 2
    • 3
  1. 1.Department of GastroenterologyUniversity of GhentGhentBelgium
  2. 2.Department of GastroenterologyHumanitas UniversityMilanItaly
  3. 3.Department of Biomedical SciencesHumanitas UniversityMilanItaly

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