Background: While therapeutic strategies able to change the natural history of inflammatory bowel diseases (IBD) are being developed, factors predicting aggressive disease are needed to be able to choose the appropriate therapeutic strategy for the individual patient based on the risk/benefit ratio. The aim of this review is to focus on the tools assisting the clinician in routine practice regarding the prediction of disease evolution. Methods: A literature review was performed, which was mainly based on PubMed search, using the following terms: Crohn's disease, ulcerative colitis, inflammatory bowel disease, genetics, serology, biomarkers, endoscopy, C-reactive protein, faecal calprotectin, disease evolution and complications. Results: For the prediction of disease evolution, clinical characteristics, particularly disease location and behaviour, are probably currently the most useful. In addition, a series of biomarkers, including genetic, serological and inflammatory markers, as well as characteristics of endoscopic lesions may have an added value. Conclusions: Simple clinical, biological and endoscopic tools may help the clinician in predicting disease evolution in IBD. However, these tools are still insufficient, and prospective evaluation of new genetic and biological markers are needed.

1.
Munkholm P, Langholz E, Davidsen M, Binder V: Disease activity courses in a regional cohort of Crohn's disease patients. Scand J Gastroenterol 1995;30:699-706.
2.
Solberg IC, Vatn MH, Høie O, Stray N, Sauar J, Jahnsen J, Moum B, Lygren I; IBSEN Study Group: Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol 2007;5:1430-1438.
3.
Peyrin-Biroulet L, Loftus EV Jr, Colombel JF, Sandborn WJ: The natural history of adult Crohn's disease in population-based cohorts. Am J Gastroenterol 2010;105:289-297.
4.
Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J: Behaviour of Crohn's disease according to the Vienna Classification: changing pattern over the course of the disease. Gut 2001;49:777-782.
5.
Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, Gendre JP: Long-term evolution of disease behavior of Crohn's disease. Inflamm Bowel Dis 2002;8:244-250.
6.
Michener WM, Whelan G, Greenstreet RL, Farmer RG: Comparison of the clinical features of Crohn's disease and ulcerative colitis with onset in childhood or adolescence. Cleve Clin Q 1982;49:13-16.
7.
Hoie O, Wolters FL, Riis L, Bernklev T, Aamodt G, Clofent J, Tsianos E, Beltrami M, Odes S, Munkholm P, Vatn M, Stockbrügger RW, Moum B; European Collaborative Study Group of Inflammatory Bowel Disease: low colectomy rates in ulcerative colitis in an unselected European cohort followed for 10 years. Gastroenterology 2007;132:507-515.
8.
Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE: Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology 2005;128:862-869.
9.
Feagan BG, Panaccione R, Sandborn WJ, D'Haens GR, Schreiber S, Rutgeerts PJ, Loftus EV Jr, Lomax KG, Yu AP, Wu EQ, Chao J, Mulani P: Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology 2008;135:1493-1499.
10.
Vernier-Massouille G, Balde M, Salleron J, Turck D, Dupas JL, Mouterde O, Merle V, Salomez JL, Branche J, Marti R, Lerebours E, Cortot A, Gower-Rousseau C, Colombel JF: Natural history of pediatric Crohn's disease: a population-based cohort study. Gastroenterology 2008;135:1106-1113.
11.
Louis E, Michel V, Hugot JP, Reenaers C, Fontaine F, Delforge M, El Yafi F, Colombel JF, Belaiche J: Early development of stricturing or penetrating pattern in Crohn's disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype. Gut 2003;52:552-557.
12.
Lakatos PL, Czegledi Z, Szamosi T, Banai J, David G, Zsigmond F, Pandur T, Erdelyi Z, Gemela O, Papp J, Lakatos L: Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease. World J Gastroenterol 2009;15:3504-3510.
13.
Henckaerts L, Van Steen K, Verstreken I, Cleynen I, Franke A, Schreiber S, Rutgeerts P, Vermeire S: Genetic risk profiling and prediction of disease course in Crohn's disease patients. Clin Gastroenterol Hepatol 2009;7:972-980.
14.
Romberg-Camps MJ, Dagnelie PC, Kester AD, Hesselink-van de Kruijs MA, Cilissen M, Engels LG, Van Deursen C, Hameeteman WH, Wolters FL, Russel MG, Stockbrügger RW: Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol 2009;104:371-383.
15.
Wolters FL, Russel MG, Sijbrandij J, Ambergen T, Odes S, Riis L, Langholz E, Politi P, Qasim A, Koutroubakis I, Tsianos E, Vermeire S, Freitas J, van Zeijl G, Hoie O, Bernklev T, Beltrami M, Rodriguez D, Stockbrügger RW, Moum B: Phenotype at diagnosis predicts recurrence rates in Crohn's disease. Gut 2006;55:1124-1130.
16.
Chow DK, Sung JJ, Wu JC, Tsoi KK, Leong RW, Chan FK: Upper gastrointestinal tract phenotype of Crohn's disease is associated with early surgery and further hospitalization. Inflamm Bowel Dis 2009;15:551-557.
17.
Hellers G, Bergstrand O, Ewerth S, Holmström B: Occurrence and outcome after primary treatment of anal fistulae in Crohn's disease. Gut 1980;21:525-527.
18.
Veloso FT, Ferreira JT, Barros L, Almeida S: Clinical outcome of Crohn's disease: analysis according to the Vienna classification and clinical activity. Inflamm Bowel Dis 2001;7:306-313.
19.
Sachar DB, Lemmer E, Ibrahim C, Edden Y, Ullman T, Ciardulo J, Roth E, Greenstein AJ, Bauer JJ: Recurrence patterns after first resection for stricturing or penetrating Crohn's disease. Inflamm Bowel Dis 2009;15:1071-1075.
20.
Greenstein AJ, Lachman P, Sachar DB, Springhorn J, Heimann T, Janowitz HD, Aufses AH Jr: Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms. Gut 1988;29:588-592.
21.
Siproudhis L, Mortaji A, Mary JY, Juguet F, Bretagne JF, Gosselin M: Anal lesions: any significant prognosis in Crohn's disease? Eur J Gastroenterol Hepatol 1997;9:235-236.
22.
Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK: Clinical features and natural history of Crohn's disease. Gastroenterology 1979;77:898-906.
23.
Bernell O, Lapidus A, Hellers G: Risk factors for surgery and postoperative recurrence in Crohn's disease. Ann Surg 2000;231:38-45.
24.
Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosenes J: Predictors of Crohn's disease. Gastroenterology 2006;130:650-656.
25.
Loly C, Belaiche J, Louis E: Predictors of severe Crohn's disease. Scand J Gastroenterol 2008;43:948-954.
26.
Wolters FL, Russel MG, Sijbrandij J, Schouten LJ, Odes S, Riis L, Munkholm P, Bodini P, O'Morain C, Mouzas IA, Tsianos E, Vermeire S, Monteiro E, Limonard C, Vatn M, Fornaciari G, Pereira S, Moum B, Stockbrügger RW; European Collaborative study group on Inflammatory Bowel Disease (EC-IBD): Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort. Gut 2006:55:447-449.
27.
Hass DJ, Brensinger CM, Lewis JD, Lichtenstein GR: The impact of increased body mass index on the clinical course of Crohn's disease. Clin Gastroenterol Hepatol 2006;4:482-488.
28.
Cosnes J, Beaugerie L, Carbonnel F, Gendre JP: Smoking cessation and the course of Crohn's disease: an intervention study. Gastroenterology 2001;120:1093-1099.
29.
Brant SR, Picco MF, Achkar JP, Bayless TM, Kane SV, Brzezinski A, Nouvet FJ, Bonen D, Karban A, Dassopoulos T, Karaliukas R, Beaty TH, Hanauer SB, Duerr RH, Cho JH: Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn's disease phenotypes. Inflamm Bowel Dis 2003;9:281-289.
30.
Seksik P, Nion-Larmurier I, Sokol H, Beaugerie L, Cosnes J: Effects of light smoking consumption on the clinical course of Crohn's disease. Inflamm Bowel Dis 2009;15:734-741.
31.
Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D'Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H; International IBD Genetics Consortium (IIBDGC), Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH: Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119-124.
32.
Annese V, Lombardi G, Perri F, D'Incà R, Ardizzone S, Riegler G, Giaccari S, Vecchi M, Castiglione F, Gionchetti P, Cocchiara E, Vigneri S, Latiano A, Palmieri O, Andriulli A: Variants of CARD15 are associated with an aggressive clinical course of Crohn's disease - an IG-IBD study. Am J Gastroenterol 2005;100:84-92.
33.
Alvarez-Lobos M, Arostegui JI, Sans M, Tassies D, Plaza S, Delgado S, Lacy AM, Pique JM, Yagüe J, Panés J: Crohn's disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence. Ann Surg 2005;242:693-700.
34.
Seiderer J, Schnitzler F, Brand S, Staudinger T, Pfennig S, Herrmann K, Hofbauer K, Dambacher J, Tillack C, Sackmann M, Göke B, Lohse P, Ochsenkühn T: Homozygosity for the CARD15 frameshift mutation 1007fs is predictive of early onset of Crohn's disease with ileal stenosis, entero-enteral fistulas, and frequent need for surgical intervention with high risk of re-stenosis. Scand J Gastroenterol 2006;41:1421-1432.
35.
Onnie CM, Fisher SA, Prescott NJ, Mirza MM, Green P, Sanderson J, Forbes A, Lewis CM, Mathew CG: Diverse effects of the CARD15 and IBD5 loci on clinical phenotype in 630 patients with Crohn's disease. Eur J Gastroenterol Hepatol 2008;20:37-45.
36.
Lesage S, Zouali H, Cézard JP, Colombel JF, Belaiche J, Almer S, Tysk C, O'Morain C, Gassull M, Binder V, Finkel Y, Modigliani R, Gower-Rousseau C, Macry J, Merlin F, Chamaillard M, Jannot AS, Thomas G, Hugot JP; EPWG-IBD Group; EPIMAD Group; GETAID Group: CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease. Am J Hum Genet 2002;70:845-857.
37.
Economou M, Trikalinos TA, Loizou KT, Tsianos EV, Ioannidis JP: Differential effects of NOD2 variants on Crohn's disease risk and phenotype in diverse populations: a metaanalysis. Am J Gastroenterol 2004;99:2393-2404.
38.
Armuzzi A, Ahmad T, Ling KL, de Silva A, Cullen S, van Heel D, Orchard TR, Welsh KI, Marshall SE, Jewell DP: Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31. Gut 2003;52:1133-1139.
39.
Vermeire S, Pierik M, Hlavaty T, Claessens G, van Schuerbeeck N, Joossens S, Ferrante M, Henckaerts L, Bueno de Mesquita M, Vlietinck R, Rutgeerts P: Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD. Gastroenterology 2005;129:1845-1853.
40.
Weersma RK, Stokkers PC, van Bodegraven AA, van Hogezand RA, Verspaget HW, de Jong DJ, van der Woude CJ, Oldenburg B, Linskens RK, Festen EA, van der Steege G, Hommes DW, Crusius JB, Wijmenga C, Nolte IM, Dijkstra G; Dutch Initiative on Crohn and Colitis (ICC): molecular prediction of disease risk and severity in a large Dutch Crohn's disease cohort. Gut 2009;58:388-395.
41.
Henckaerts L, Van Steen K, Verstreken I, Cleynen I, Franke A, Schreiber S, Rutgeerts P, Vermeire S: Genetic risk profiling and prediction of disease course in Crohn's disease patients. Clin Gastroenterol Hepatol 2009;7:972-980.
42.
Targan SR, Landers CJ, Yang H, Lodes MJ, Cong Y, Papadakis KA, Vasiliauskas E, Elson CO, Hershberg RM: Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. Gastroenterology 2005;128:2020-2028.
43.
Arnott ID, Landers CJ, Nimmo EJ, Drummond HE, Smith BK, Targan SR, Satsangi J: Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol 2004;99:2376-2384.
44.
Papp M, Altorjay I, Dotan N, Palatka K, Foldi I, Tumpek J, Sipka S, Udvardy M, Dinya T, Lakatos L, Kovacs A, Molnar T, Tulassay Z, Miheller P, Norman GL, Szamosi T, Papp J; Hungarian IBD Study Group, Lakatos PL: New serological markers for inflammatory bowel disease are associated with earlier age at onset, complicated disease behavior, risk for surgery, and NOD2/CARD15 genotype in a Hungarian IBD cohort. Am J Gastroenterol 2008;103:665-681.
45.
Dubinsky MC, Kugathasan S, Mei L, Picornell Y, Nebel J, Wrobel I, Quiros A, Silber G, Wahbeh G, Katzir L, Vasiliauskas E, Bahar R, Otley A, Mack D, Evans J, Rosh J, Hemker MO, Leleiko N, Crandall W, Langton C, Landers C, Taylor KD, Targan SR, Rotter JI, Markowitz J, Hyams J; Western Regional Pediatric IBD Research Alliance; Pediatric IBD Collaborative Research Group; Wisconsin Pediatric IBD Alliance: Increased immune reactivity predicts aggressive complicating Crohn's disease in children. Clin Gastroenterol Hepatol 2008;6:1105-1111.
46.
Amre DK, Lu SE, Costea F, Seidman EG: Utility of serological markers in predicting the early occurrence of complications and surgery in pediatric Crohn's disease patients. Am J Gastroenterol 2006;101:645-652.
47.
Lee JC, Lyons PA, McKinney EF, Sowerby JM, Carr EJ, Bredin F, Rickman HM, Ratlamwala H, Hatton A, Rayner TF, Parkes M, Smith KGC: Gene expression profiling of CD8+ T cells predicts prognosis in patients with Crohn disease and ulcerative colitis. J Clin Invest 2011;121:4170-4179.
48.
Allez M, Lemann M, Bonnet J, Cattan P, Jian R, Modigliani R: Long term outcome of patients with active Crohn's disease exhibiting extensive and deep ulcerations at colonoscopy. Am J Gastroenterol 2002;97:947-953.
49.
Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M: Predictability of the postoperative course of Crohn's disease. Gastroenterology 1990;99:956-963.
50.
Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S, D'Haens G; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club: Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn's disease. Gastroenterology 2010;138:463-468.
51.
Louis E, Vernier-Massouille G, Grimaud J, Bouhnik Y, Laharie D, Dupas JL, et al: Infliximab discontinuation in Crohn's disease patients in stable remission of combined therapy with immunosuppressors: interim analysis of a prospective cohort study. Gut 2008;57(sII):A66.
52.
Solberg IC, Lygren I, Jahnsen J, Aadland E, Høie O, Cvancarova M, Bernklev T, Henriksen M, Sauar J, Vatn MH, Moum B; IBSEN Study Group: Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol 2009;44:431-440.
53.
Langholz E, Munkholm P, Davidsen M, Binder V: Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 1992;103:1444-1451.
54.
Devroede GJ, Taylor WF, Sauer WG, Jackman RJ, Stickler GB: Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 1971;285:17-21.
55.
Ekbom A, Helmick CG, Zack M, Holmberg L, Adami HO: Survival and causes of death in patients with inflammatory bowel disease: a population-based study. Gastroenterology 1992;103:954-960.
56.
Lakatos L, Mester G, Erdelyi Z, David G, Pandur T, Balogh M, et al: Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a population-based study. Inflamm Bowel Dis 2006;12:205-211.
57.
Jess T, Loftus EV Jr, Velayos FS, Harmsen WS, Zinsmeister AR, Smyrk TC, Schleck CD, Tremaine WJ, Melton LJ 3rd, Munkholm P, Sandborn WJ: Risk of intestinal cancer in inflammatory bowel disease: a population-based study from Olmsted County, Minnesota. Gastroenterology 2006;130:1039-1046.
58.
Etchevers MJ, Aceituno M, García-Bosch O, Ordás I, Sans M, Ricart E, Panés J: Risk factors and characteristics of extent progression in ulcerative colitis. Inflamm Bowel Dis 2009;15:1320-1325.
59.
Gower-Rousseau C, Dauchet L, Vernier-Massouille G, Tilloy E, Brazier F, Merle V, Dupas JL, Savoye G, Baldé M, Marti R, Lerebours E, Cortot A, Salomez JL, Turck D, Colombel JF: The natural history of pediatric ulcerative colitis: a population-based cohort study. Am J Gastroenterol 2009;104:2080-2088.
60.
Boyko EJ, Perera DR, Koepsell TD, Keane EM, Inui TS: Effects of cigarette smoking on the clinical course of ulcerative colitis. Scand J Gastroenterol 1988;23:1147-1152.
61.
Beaugerie L, Massot N, Carbonnel F, Cattan S, Gendre JP, Cosnes J: Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol 2001;96:2113-2116.
62.
Szamosi T, Banai J, Lakatos L, Czegledi Z, David G, Zsigmond F, Pandur T, Erdelyi Z, Gemela O, Papp M, Papp J, Lakatos PL: Early azathioprine/biological therapy is associated with decreased risk for first surgery and delays time to surgery but not reoperation in both smokers and nonsmokers with Crohn's disease, while smoking decreases the risk of colectomy in ulcerative colitis. Eur J Gastroenterol Hepatol 2010;22:872-879.
63.
Satsangi J, Welsh KI, Bunce M, Julier C, Farrant JM, Bell JI, Jewell DP: Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 1996;347:1212-1217.
64.
Ahmad T, Armuzzi A, Neville M, Bunce M, Ling KL, Welsh KI, Marshall SE, Jewell DP: The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis. Tissue Antigens 2003;62:527-535.
65.
Fleshner PR, Vasiliauskas EA, Kam LY, Fleshner NE, Gaiennie J, Abreu-Martin MT, Targan SR: High level perinuclear antineutrophil cytoplasmic antibody (pANCA) in ulcerative colitis patients before colectomy predicts the development of chronic pouchitis after ileal pouch-anal anastomosis. Gut 2001;49:671-677.
66.
Fleshner P, Ippoliti A, Dubinsky M, Vasiliauskas E, Mei L, Papadakis KA, Rotter JI, Landers C, Targan S: Both preoperative perinuclear antineutrophil cytoplasmic antibody and anti-CBir1 expression in ulcerative colitis patients influence pouchitis development after ileal pouch-anal anastomosis. Clin Gastroenterol Hepatol 2008;6:561-568.
67.
Melmed GY, Fleshner PR, Bardakcioglu O, Ippoliti A, Vasiliauskas EA, Papadakis KA, Dubinsky M, Landers C, Rotter JI, Targan SR: Family history and serology predict Crohn's disease after ileal pouch-anal anastomosis for ulcerative colitis. Dis Colon Rectum 2008;51:100-108.
68.
Carbonnel F, Lavergne A, Lémann M, Bitoun A, Valleur P, Hautefeuille P, Galian A, Modigliani R, Rambaud JC: Colonoscopy of acute colitis. A safe and reliable tool for assessment of severity. Dig Dis Sci 1994;39:1550-1557.
69.
Wright R, Truelove SR: Serial rectal biopsy in ulcerative colitis during the course of a controlled therapeutic trial of various diets. Am J Dig Dis 1966;11:847-857.
70.
Rutgeerts P, Sandborn WJ, Feagan BG, Reinisch W, Olson A, Johanns J, Travers S, Rachmilewitz D, Hanauer SB, Lichtenstein GR, de Villiers WJ, Present D, Sands BE, Colombel JF: Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476.
71.
Frøslie KF, Jahnsen J, Moum BA, Vatn MH; IBSEN Group: Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 2007;133:412-422.
72.
Ferrante M, Vermeire S, Fidder H, Schnitzler F, Noman M, Van Assche G, et al: Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis 2008;2:219-225.
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