• Aucun résultat trouvé

Does the phenotype at diagnosis (e.g., fibrostenosing, inflammatory, perforating) predict the course of Crohn's disease?

N/A
N/A
Protected

Academic year: 2021

Partager "Does the phenotype at diagnosis (e.g., fibrostenosing, inflammatory, perforating) predict the course of Crohn's disease?"

Copied!
3
0
0

Texte intégral

(1)

Does the phenotype at diagnosis (eg. Fibrostenosing, inflammatory,

perforating) predict the course of Crohn’s disease?

Edouard Louis, Catherine Reenaers, Jacques Belaiche.

Department of Gastroenterology CHU Liège, GIGA research University of Liège, and FNRS, Belgium.

To answer this question, we must first define Crohn’s disease phenotypes, define Crohn’s disease course, consider how phenotype at diagnosis could influence disease course, and finally see whether any data have been published suggesting such influence.

Phenotypes of Crohn’s disease

Crohn’s disease is characterized by a chronic inflammatory reaction of the bowel wall. This abnormal inflammation is usually transmural, and involves immunoinflammatory cells as well as non immune cells, such as fibroblasts and endothelial cells. Some of these cells exhibit resistance to apoptosis, maintaining the inflammatory reaction, and they produce a broad range of cytokines. These cytokines induce the production of proteases, metalloproteinases and growth factors involved in tissue remodelling. In some cases, this remodelling will end up with an intestinal stricture, characterized by mucosal and submucosal fibrosis, with abnormal collagen deposition, as well as muscular hyperplasia. In other cases, penetrating lesions may develop, in which deep fissures give rise to covert perforation, para-intestinal abscess, free perforation or fistula. A fibrostenosing phenotype is characterized by the presence of clinically-significant strictures giving rise to occlusive or subocclusive symptoms. A perforating phenotype is characterized by penetrating lesions. These can originate from the intestine, and give rise not only to entero-enteric, enterocutaneous, or entero-hollow organ fistula, but also to paraintestinal abscesses, infiltrations or seldom peritonitis. These

abdominal fistulizing lesion originate most of the time just upstream or at the beginning of a stricture and may thus be considered as a further complication of these stricturing lesions (1,2). This suggests that an increase in luminal pressure and parietal tension is a major favouring factor for these lesions. They also can originate from the anal canal, ano-rectal junction or lower rectum and give rise to all the simple or complex lesions characterizing perianal Crohn’s disease. In this case the anal sphincter probably plays a role equivalent to a stricture, as a favouring factor for perforating lesions. Although initially classified in the same phenotype of perforating Crohn’s disease (3), penetrating intraabdominal disease rather rarely coexists with perianal disease (4). This is probably due to the fact that these subphenotypes are related to different locations of the disease. Therefore in the last proposed classification for Crohn’s disease, these two subphenotypes were put separately (5). An inflammatory phenotype is characterized by the absence of such perforating or fibrostenosing complication. The phenotype of Crohn’s disease is not an independent and isolated parameter. Beside the possible influence of endogenous (genetic influence on the inflammatory reaction and tissue remodelling) and exogenous (suggested influence of smoking) factors, the phenotype at diagnosis will depend on several more trivial parameters, such as the delay between

symptoms and diagnosis or the location of the disease, strictures for example developing more often in the small intestine than in the colon.

Course of Crohn’s disease

The course of Crohn’s disease can be defined by several major events. The intensity and the extent as well as location of inflammation will determine the intensity of the flares of the disease. Together with this, the frequency of the flares and the intestinal (participating in the

(2)

definition of the phenotype) or extra-intestinal complications that will develop will influence the type of treatment, particularly the need for immuno-suppression, biological therapies or surgery. All these factors may lead to major often irreversible consequences, such as very severe and complex perianal lesions, intestinal stoma, extended intestinal resections and short bowel syndrome, or even death. These final consequences, but also, the number and severity of flares, the complications developed and the treatments used, including surgery, all

contribute to any characterization of the course of the disease.

Influence of phenotype on the course of Crohn’s disease

The phenotype of the disease can influence the course of the disease, since a fibrostenosing or a perforating phenotype is already the sign of the presence of a complication. By itself, a particular phenotype may already necessitate a surgery or will motivate the use of

immunosuppressive drugs. Beyond this, the predictive value of the phenotype at diagnosis is more difficult to imagine. One of the reasons is that the phenotype of Crohn’s disease is a dynamic process and that after 10 years almost one half of the patients with an inflammatory phenotype at diagnosis will develop fibrostenosing or perforating complications that will affect the course of the disease (4). However, it must be remembered that only a minority of Crohn’s disease patients will remain complication-free over time (30% at 10 years and less than 20% at 20 years), and that among patients developing complications, these will occur with a variable delay after diagnosis. This can be interpreted as a different inclination to develop such complications, namely patients having complications already at diagnosis being the most prone to develop future complications. This difference may then influence the course of the disease.

A systematic med-line search for studies on “natural history” or “disease course” of Crohn’s disease together with a possible influence of disease phenotype on these parameters disclosed rather few relevant studies. The presence at diagnosis, of perianal lesions, has been associated with a more frequent use of immunosuppressive treatment (6,7), poor mid-term outcome (8), increased risk of surgical resection and post-operative recurrence (9). An intra-abdominal penetrating behaviour has been associated with more frequent abdominal surgeries (6).Other studies have also shown that an abdominal penetrating behaviour at the time of first surgery was associated with a more rapid recurrence and usually again an abdominal penetrating disease as an indication of further surgery (10). Pure fibrostenosing disease is present at diagnosis in about 10% of cases and may reach 20-30% after 10 years (4). Few patients seem to develop pure fibrostenosing disease beyond 10 years (4). When a fibrostenosing disease has not been associated with penetrating complication after 2-3 years, it tends to remain pure fibrostenosing disease over time (4).

More recently, some works have been performed attempting at defining predictive factors for the development of disabling or severe disease over time. In a first study on a large cohort, using both retrospective analysis and prospective validation, an assessment of factors present at diagnosis and associated with the further development of disabling disease defined by chronic symptoms, the need for surgery, immunosuppressive treatments, biologicals, and hospitalisations, disclosed a perianal disease together with young age at diagnosis and the need for steroids to treat the first flare, as factors associated with such disabling disease (11). In a second study, these factors were partly confirmed, particularly the presence of a perianal disease at diagnosis (12). Furthermore, the presence of a stricturing or a penetrating disease at diagnosis, and the presence of perianal disease together with weigth loss, fever and increased platelet count were associated with the further development of a severe disease defined by the surgical resection of two small bowel segments (or at least 70 cm), surgical resection of any colonic segment, complex perianal disease or a definitive stoma (12). However in a European

(3)

population-based study, a stricturing or a penetrating behaviour at diagnosis were not

associated with further recurrence after the first flare, need for surgery (13) or with increased mortality (14).

In conclusion, although the phenotype of Crohn’s disease is of a dynamic character, the phenotype at diagnosis may help to predict disease course over time. Particularly, the presence of perianal disease, and to a lesser extent an intraabdominal perforating or a stricturing disease, have been associated with poorer outcome in several studies.

1. Kelly JK, Preshaw RM. Origin of fistulas in Crohn’s disease. J Clin Gastroenterol 1989; 11: 193-196.

2. Tonelli P. Perforation in Crohn’s ileitis and its impact on the natural history of the disease. Note 1. Pathogenic process of the event, its relationship with intestinal obstruction, and its immediate consequences. Ann Ital Chir 1995; 66: 335-347. 3. Gasche C, Scholmerich J, Brynskov J, et al. A simple classification of Crohn’s

disease: report of the working party of the world congresses of gastroenterology, Vienna 1998. Inflamm Bowel Dis 2000; 6: 8-15.

4. Louis E, Collard A, Oger AF, et al. Behaviour of Crohn’s disease according to the Vienna Classification: changing pattern over the course of the disease. Gut 2001; 49: 777-782.

5. Silverberg M, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a working party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol 2005; 19 (suppl A): 5A-36A.

6. 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.

7. 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.

8. Mekhjian HS, Switz DM, Melnyk CS, Rankin GB, Brooks RK. Clinical features and natural history of Crohn’s disease. Gastroenterology 1979; 77: 898-906.

9. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg 2000; 231: 38-45.

10. 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.

11. Beaugerie L, Seksik P, Nion-Larmurier I, et al. Predictors of Crohn’s disease. Gastroenterology 2006; 130: 650-656.

12. Loly C, Belaiche J, Louis E. Predictors of severe Crohn’s disease. Scand J Gastroenterol 2008. In press.

13. Wolters FL, Russel MG, Sijbrandij J, et al. Phenotype at diagnosis predicts recurrence rates in Crohn’s disease. Gut 2006; 55: 1124-1130.

14. Wolters FL, Russel MG, Sijbrandij J, et al. Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort. Gut 2006: 55: 447-449.

Références

Documents relatifs

Our study shows that (i) Hypoxia may modify the adipo- genic metabolism of primary human adipose cells; (ii) Toxicity of NRTI depends of oxygen environment of adi- pose cells; and

PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives fund- ing from Fight for Sight (UK), the Isaac

Deuxième méthode : toutes les minutes on prélève dans R un pourcentage fixe q de mélange que l’on remplace par la même quantité de L ne contenant pas S... Etudier les variations

Real-time RT-PCR results were normalized using L27 as a reference gene and are shown as average expression fold change (± SEM) values obtained from three experiments, each conducted

prausnitzii and Its Supernatant Induce an Increased Secretion of IL-10 and a Decreased Secretion of TNF- ␣ and IL-12 in TNBS- Induced Colitis in Mice.. Forty-eight hours after

Mycobacterium tuberculosis Virulent Factor ESAT-6 Drives Macrophage Differentiation Toward the Pro-inflammatory M1 Phe- notype and Subsequently Switches It to the Anti-inflammatory

Thus, the localization of the B4GALNT2 gene within the minimal locus, the presence of the SNP g.36938224T.A on OAR11, localized in the intron 7 of this gene as the possible

Dans le cadre de ce stage, nous nous intéressons au lien éventuel entre la présence d’un ensemble de micro-habitats sur la biodiversité de 3 groupes