Introductory Chapter: Crohn’s Disease – The Current State of the Art

1. Introduction

Crohn’s disease (CD) is a form of inflammatory bowel disease (IBD) which is differentiated from Ulcerative colitis (UC) by its patchy and full thickness inflammation which can affect anywhere from mouth to anus. The diagnosis can be challenging in CD compared to UC due to isolated involvement of deep small bowel along with various infectious and non-infectious mimics leading to diagnostic dilemma. The current diagnostic modalities have evolved from fiberoptic endoscopy to capsule endoscopy, motorized spiral enteroscopy and even artificial intelligence assisted diagnosis from endoscopic/intestinal ultrasound images. Left untreated, it can lead to mechanical complications such as strictures and fistulas which need surgical therapy or interventional endoscopic therapies. Unlike the other counterpart (UC), CD is notorious to cause post-operative recurrence of the disease in a vast majority of the patients over time if appropriate prophylactic therapies are not initiated.

2. History of Crohn’s disease

The first series of “Chronic interstitial enteritis”, currently known as Crohn’s disease (CD) was first reported by Scottish surgeon named Thomas Kennedy Dalziel in British Medical Journal in 1913 [1]. Nearly 20 years later in 1932, Burrill B. Crohn, Leon Ginzburg and Gordon D. Oppenheimer published the description of 14 cases of “regional enteritis” in Journal of American Medical Association [2]. According to Ginsberg, he and Oppenheimer collected 12 cases and wrote most of the manuscript and were put in touch with Crohn by the pathologist Paul Klemperer to increase the number of cases. Crohn was given the manuscript and they did not hear from him again until its was published with Crohn’s name as the lead. That is how the eponym of CD was ascribed to Crohn [3]. In the next 20 years, it was recognized that CD can involve any part of the bowel apart from classical description in the ileum [3]. Since then several therapeutic and technological advances have taken place in the diagnosis and management of CD.

3. The rising burden of the disease

IBD is emerging in the developing countries where sporadic cases are reported whereas in newly industrialized countries, there is acceleration in incidence but prevalence is still low. Western countries are in stage of compounding prevalence where incidence is stable but prevalence is increasing. This is due to chronic, lifelong nature of disease with low mortality. The Western countries may soon enter a stage of prevalence equilibrium in which there is balance between aging population and IBD incidence [4]. Industrialization, changing lifestyle and westernization are implicated in the rapid rise in newly industrialized countries. This gives us the opportunity to investigate the cause of the rising incidence. Epidemiological trends suggest that the rising burden of CD follows that of UC in areas where IBD is emerging [4].

4. Gut microbiome in Crohn’s disease

Reduction in gut microbial diversity have been implicated in pathogenesis of CD and hence intestinal microbiota manipulation strategies have been studied as a treatment option.

Fecal microbiota transplant has not been shown to be effective in CD unlike UC. Dietary manipulation have been extensively studied although the certainty of the evidence remains low. There is emerging data on the role of partial enteral nutrition in induction and prevention of relapse in CD similar to exclusive enteral nutrition. Mediterranean diet is similar to specific carbohydrate diet although the certainty of evidence remains low [5]. A better understanding of host and microbiota interaction is warranted [6]. Currently these therapies can be used as an adjunctive therapy rather than standalone management of CD.

5. Evolution of small bowel endoscopic imaging in CD

Isolated small bowel involvement can be seen in a third of patients with CD. Although terminal ileum is involved in the majority, isolated proximal small bowel involvement is not uncommon. Small bowel evaluation have evolved from video capsule endoscopy (VCE) and balloon assisted enteroscopy to currently the motorized spiral enteroscopy. Several technological modifications of VCE have been improved the technology including patency capsule, double head capsule, three-dimensional reconstruction, sampling system, panoramic view (344 and 360 degree lateral) capsule, pan-enteric capsule, use of softwares and artificial intelligence (to reduce capsule reading time).

6. Pregnancy, fertility, sexuality and interdisciplinary management of perianal fistula

CD has been associated with higher risk of preterm delivery, small for gestational age, low birth weight and stillbirth but no increased risk of congenital abnormalities [7]. Control of disease activity is of prime importance to achieve optimal maternal and neonatal outcomes. Fertility can be decreased by disease activity, medications (male) and pelvic surgery (female). Same factors including extra-intestinal manifestations of disease can influence sexuality [8].

The management of perianal CD need multidisciplinary approach with IBD specialist, surgeon, radiologist and recently stem cell based therapies.

7. Evolution of Crohn’s disease

Over the last century, IBD including CD has evolved from clinical observations to a network of advance therapies and quality of care (Figure 1). From the disease classification, we have moved from disease phenotypes towards genetics, immunologic typing and recently environmental typing based on microbiome. The treatments have evolved from empirical therapies to evidence based therapies, disease modifying agents and treat to target strategy to alter the natural history of the disease. Lastly we have moved from organizational funding research to collaborative efforts to understand the global phenomenon of this emerging disease. In this book, we shall focus on the various aspects of the latest development in Crohn’s disease specially diagnosis, gut microbiome, small bowel capsule endoscopy and managing pregnancy.

Figure 1.

Evolution of Crohn’s disease from clinical observations to diverse diagnostic modalities and a network of advanced therapies. ASA-amino salicylic acid, ADA-adalimumab, IFX-infliximab, NTZ-natalizumab, VDZ-vedolizumab, UST-ustekinumab.