15 Inflammatory Bowel Disease: a complex and heterogeneous disease Inflammatory bowel diseases (IBD) are chronic ulcerative inflammatory diseases of the gastrointestinal (GI) tract, characterized by a considerable degree of heterogeneity and pathophysiological complexity.1 Crohn’s disease (CD) and ulcerative colitis (UC) are the two main clinicopathological subtypes of IBD. In CD, ulcerations and inflammation can occur in any part of the gastrointestinal (GI) tract, whereas in UC, inflammation is generally limited to the colon. CD is endoscopically characterized by discontinuous or ‘patchy’ involvement, ulcerative inflammation (where the terminal ileum is most frequently affected), a ‘cobblestone appearance’ of the intestines, and (peri-)anal lesions, whereas UC typically presents with rather superficial mucosal inflammation.2,3 Currently, IBD affects approximately 1 in 1,000 individuals, and its global incidence is steadily rising, especially in European and North American countries. This trend is fairly similar for men and women, but shows varying patterns depending on genetic background.4 The peak age of onset lies within the second to fourth decade of life. Although the exact disease origin is unknown, an interplay between genetic factors, the gut microbiota, the host immune system and environmental triggers (e.g. lifestyle and diet) is believed to underlie the initiation of IBD.5,6 Clinical manifestations of IBD include abdominal pain, diarrhoea (with or without blood loss), fatigue, weight loss, and a series of extraintestinal manifestations, e.g. arthralgia or arthritis, uveitis, and skin abnormalities. However, clinical symptoms of IBD vary greatly between patients and in time. This heterogeneous clinical symptomatology makes a clinical suspicion of IBD rather nonspecific, which may lead to a delay in medical diagnosis and necessitates the use of additional diagnostic modalities. According to the European Crohn’s and Colitis Organisation (ECCO) and European Society of Gastrointestinal and Abdominal Radiology (ESGAR) diagnostic consensus guidelines, the diagnosis of CD or UC should be based on a combination of clinical, biochemical, stool, endoscopic, cross-sectional imaging, and histological investigations.7 Upon initial investigations of a patient presenting with GI complaints and a raised inflammatory marker in stool, the performance of an invasive ileo-colonoscopy (i.e., endoscopy) procedure with biopsies is considered as the gold standard for diagnosing IBD. The disease course of patients with IBD is characterised by a ‘relapse-remitting’ pattern, where episodes ofmilddisease, sometimes in the absence of any symptoms, alternatewithperiods of active and/or severe disease, which often require urgent medical or surgical intervention. Therapeutic interventions are aimed at resolving intestinal inflammation, maintaining disease remission, and preventing long-term disease complications, hospitalisation and the need for surgery. Despite the increasing availability of effective treatments, it remains challenging to control the disease course. This is evidenced by the fact that long-term surgery rates only slightly decreased over the past decade; even up to one third of patients require surgery within the first ten years post-diagnosis.8 As a consequence, patients with IBD still need life-long treatment. The need for biomarker-based disease evaluation of IBD The term ‘biomarker’ is defined as “A characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention”.9,10 In the context of IBD, biomarkers could potentially be used for a variety of disease management purposes (Figure 1), many of which will be touched upon in subsequent sections. General introduction and outline of the thesis
RkJQdWJsaXNoZXIy MjY0ODMw