Disease Behavior in Adult Patients: Are There Predictors for Stricture or Fistula Formation?

In the current era, in inflammatory bowel disease step-up vs. top-down therapeutic approaches for the treatment of Crohn's disease (CD) are evaluated. As a consequence, we need to be able to differentiate between patients who will have more aggressive phenotypes to those with potentially more benign CD course. The former would require closer follow-up; however, more important might be the subgroup of patients to whom we want to offer biologic and immunomodulator therapy early on. This strategy is the only one supposed to prevent hospitalization and surgical intervention, specifically in patients with fistulae. Patients with expected fibrostenotic disease phenotype require early identification as well. The data regarding primary prevention of fibrostenosis are scarce; however, the association of biologic therapy with fewer surgeries might suggest that at least a subgroup of these patients would benefit from early, step-up therapeutic strategy. They might also benefit more from early immunomodulator therapy, as this was shown to have a secondary (though modest) preventive effect. The patients with fibrostenotic phenotype are also candidates for the most needed but still practically nonexistent anti-fibrotic therapies. In any case where patients are identified as having a higher chance to develop the more aggressive phenotypes, fibrostenotic and perforating, recommendation to avoid triggers/accelerators of disease progression (smoking, NSAIDS use) should be kept rigorously. Until recently, we based our attempts to predict disease phenotype mainly on clinical characteristics. As would be the case with many clinical features, some of them are not even predictors, but already manifestations of the condition we are trying to predict. Intervention at this stage might be too late for this patient. In addition to known demographic and clinical predictors reported, more recently sophisticated predictors shall be described. These predictors belong to three major groups: serologic markers, genetic markers, mucosal disease/healing. The major serologic markers used: anti-Saccharomyces cerevisiae antibodies (ASCA), anti-neutrophil cytoplasmic antibodies (ANCA), outer membrane porin C (OmpC), CBir1-flagellin, antibodies against I2 protein and the anti-glycan antibodies: anti-laminaribioside carbohydrate (ALCA), anti-chitobioside carbohydrate (ACCA) and anti-mannobioside carbohydrate (AMCA) and their associations with penetrating and fibrostenotic disease shall be discussed. The associations of genetic polymorphisms such as CARD15 and TLR4 variants and more aggressive disease phenotype will be described as well. Finally, the data supporting the relationship between inflamed, in contrast to healed intestinal mucosa and more aggressive disease course will be illustrated. These predictors may be used in clinical practice and/or research in order to better stratify CD prognosis. Thus they may be significant in our therapeutic decisions. Models for using these predictors would be presented.